Science.gov

Sample records for dynamic signal analyses

  1. Real-time single-molecule co-immunoprecipitation analyses reveal cancer-specific Ras signalling dynamics

    PubMed Central

    Lee, Hong-Won; Kyung, Taeyoon; Yoo, Janghyun; Kim, Tackhoon; Chung, Chaeuk; Ryu, Ji Young; Lee, Hanki; Park, Kihyun; Lee, Sangkyu; Jones, Walton D.; Lim, Dae-Sik; Hyeon, Changbong; Do Heo, Won; Yoon, Tae-Young

    2013-01-01

    Co-immunoprecipitation (co-IP) has become a standard technique, but its protein-band output provides only static, qualitative information about protein–protein interactions. Here we demonstrate a real-time single-molecule co-IP technique that generates real-time videos of individual protein–protein interactions as they occur in unpurified cell extracts. By analysing single Ras–Raf interactions with a 50-ms time resolution, we have observed transient intermediates of the protein–protein interaction and determined all the essential kinetic rates. Using this technique, we have quantified the active fraction of native Ras proteins in xenograft tumours, normal tissue and cancer cell lines. We demonstrate that the oncogenic Ras mutations selectively increase the active-Ras fraction by one order of magnitude, without affecting total Ras levels or single-molecule signalling kinetics. Our approach allows us to probe the previously hidden, dynamic aspects of weak protein–protein interactions. It also suggests a path forward towards precision molecular diagnostics at the protein–protein interaction level. PMID:23422673

  2. Genetic Analyses of Integrin Signaling

    PubMed Central

    Wickström, Sara A.; Radovanac, Korana; Fässler, Reinhard

    2011-01-01

    The development of multicellular organisms, as well as maintenance of organ architecture and function, requires robust regulation of cell fates. This is in part achieved by conserved signaling pathways through which cells process extracellular information and translate this information into changes in proliferation, differentiation, migration, and cell shape. Gene deletion studies in higher eukaryotes have assigned critical roles for components of the extracellular matrix (ECM) and their cellular receptors in a vast number of developmental processes, indicating that a large proportion of this signaling is regulated by cell-ECM interactions. In addition, genetic alterations in components of this signaling axis play causative roles in several human diseases. This review will discuss what genetic analyses in mice and lower organisms have taught us about adhesion signaling in development and disease. PMID:21421914

  3. Mutational Analyses of HAMP Helices Suggest a Dynamic Bundle Model of Input-Output Signaling in Chemoreceptors

    PubMed Central

    Zhou, Qin; Ames, Peter; Parkinson, John S.

    2009-01-01

    SUMMARY To test the gearbox model of HAMP signaling in the E. coli serine receptor, Tsr, we generated a series of amino acid replacements at each residue of the AS1 and AS2 helices. The residues most critical for Tsr function defined hydrophobic packing faces consistent with a 4-helix bundle. Suppression patterns of helix lesions conformed to the the predicted packing layers in the bundle. Although the properties and patterns of most AS1 and AS2 lesions were consistent with both proposed gearbox structures, some mutational features specifically indicate the functional importance of an x-da bundle over an alternative a-d bundle. These genetic data suggest that HAMP signaling could simply involve changes in the stability of its x-da bundle. We propose that Tsr HAMP controls output signals by modulating destabilizing phase clashes between the AS2 helices and the adjoining kinase control helices. Our model further proposes that chemoeffectors regulate HAMP bundle stability through a control cable connection between the transmembrane segments and AS1 helices. Attractant stimuli, which cause inward piston displacements in chemoreceptors, should reduce cable tension, thereby stabilizing the HAMP bundle. This study shows how transmembrane signaling and HAMP input-output control could occur without the helix rotations central to the gearbox model. PMID:19656294

  4. Nonlinear structural crash dynamics analyses

    NASA Technical Reports Server (NTRS)

    Hayduk, R. J.; Thomson, R. G.; Wittlin, G.; Kamat, M. P.

    1979-01-01

    Presented in this paper are the results of three nonlinear computer programs, KRASH, ACTION and DYCAST used to analyze the dynamic response of a twin-engine, low-wing airplane section subjected to a 8.38 m/s (27.5 ft/s) vertical impact velocity crash condition. This impact condition simulates the vertical sink rate in a shallow aircraft landing or takeoff accident. The three distinct analysis techniques for nonlinear dynamic response of aircraft structures are briefly examined and compared versus each other and the experimental data. The report contains brief descriptions of the three computer programs, the respective aircraft section mathematical models, pertinent data from the experimental test performed at NASA Langley, and a comparison of the analyses versus test results. Cost and accuracy comparisons between the three analyses are made to illustrate the possible uses of the different nonlinear programs and their future potential.

  5. Deblurring Signal Network Dynamics.

    PubMed

    Kamps, Dominic; Dehmelt, Leif

    2017-09-15

    To orchestrate the function and development of multicellular organisms, cells integrate intra- and extracellular information. This information is processed via signal networks in space and time, steering dynamic changes in cellular structure and function. Defects in those signal networks can lead to developmental disorders or cancer. However, experimental analysis of signal networks is challenging as their state changes dynamically and differs between individual cells. Thus, causal relationships between network components are blurred if lysates from large cell populations are analyzed. To directly study causal relationships, perturbations that target specific components have to be combined with measurements of cellular responses within individual cells. However, using standard single-cell techniques, the number of signal activities that can be monitored simultaneously is limited. Furthermore, diffusion of signal network components limits the spatial precision of perturbations, which blurs the analysis of spatiotemporal processing in signal networks. Hybrid strategies based on optogenetics, surface patterning, chemical tools, and protein design can overcome those limitations and thereby sharpen our view into the dynamic spatiotemporal state of signal networks and enable unique insights into the mechanisms that control cellular function in space and time.

  6. Signaling dynamics and peroxisomes.

    PubMed

    Mast, Fred D; Rachubinski, Richard A; Aitchison, John D

    2015-08-01

    Peroxisomes are remarkably responsive organelles. Their composition, abundance and even their mechanism of biogenesis are influenced strongly by cell type and the environment. This plasticity underlies peroxisomal functions in metabolism and the detoxification of dangerous reactive oxygen species. However, peroxisomes are integrated into the cellular system as a whole such that they communicate intimately with other organelles, control signaling dynamics as in the case of innate immune responses to infectious disease, and contribute to processes as fundamental as longevity. The increasing evidence for peroxisomes having roles in various cellular and organismal functions, combined with their malleability, suggests complex mechanisms operate to control cellular dynamics and the specificity of cellular responses and functions extending well beyond the peroxisome itself. A deeper understanding of the functions of peroxisomes and the mechanisms that control their plasticity could offer opportunities for exploiting changes in peroxisome abundance to control cellular function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Wavelet-Based Multiresolution Analyses of Signals

    DTIC Science & Technology

    1992-06-01

    classification. Some signals, notably those of a transient nature, are inherently difficult to analyze with these traditional tools. The Discrete Wavelet Transform has...scales. This thesis investigates dyadic discrete wavelet decompositions of signals. A new multiphase wavelet transform is proposed and investigated. The

  8. Inelastic and Dynamic Fracture and Stress Analyses

    NASA Technical Reports Server (NTRS)

    Atluri, S. N.

    1984-01-01

    Large deformation inelastic stress analysis and inelastic and dynamic crack propagation research work is summarized. The salient topics of interest in engine structure analysis that are discussed herein include: (1) a path-independent integral (T) in inelastic fracture mechanics, (2) analysis of dynamic crack propagation, (3) generalization of constitutive relations of inelasticity for finite deformations , (4) complementary energy approaches in inelastic analyses, and (5) objectivity of time integration schemes in inelastic stress analysis.

  9. Dynamics in atomic signaling games.

    PubMed

    Fox, Michael J; Touri, Behrouz; Shamma, Jeff S

    2015-07-07

    We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss.

  10. Optimal temporal patterns for dynamical cellular signaling

    NASA Astrophysics Data System (ADS)

    Hasegawa, Yoshihiko

    2016-11-01

    Cells use temporal dynamical patterns to transmit information via signaling pathways. As optimality with respect to the environment plays a fundamental role in biological systems, organisms have evolved optimal ways to transmit information. Here, we use optimal control theory to obtain the dynamical signal patterns for the optimal transmission of information, in terms of efficiency (low energy) and reliability (low uncertainty). Adopting an activation-deactivation decoding network, we reproduce several dynamical patterns found in actual signals, such as steep, gradual, and overshooting dynamics. Notably, when minimizing the energy of the input signal, the optimal signals exhibit overshooting, which is a biphasic pattern with transient and steady phases; this pattern is prevalent in actual dynamical patterns. We also identify conditions in which these three patterns (steep, gradual, and overshooting) confer advantages. Our study shows that cellular signal transduction is governed by the principle of minimizing free energy dissipation and uncertainty; these constraints serve as selective pressures when designing dynamical signaling patterns.

  11. Static and dynamic analyses of tensegrity structures

    NASA Astrophysics Data System (ADS)

    Nishimura, Yoshitaka

    Tensegrity structures are a class of truss structures consisting of a continuous set of tension members (cables) and a discrete set of compression members (bars). Since tensegrity structures are light weight and can be compactly stowed and deployed, cylindrical tensegrity modules have been proposed for space structures. From a view point of structural dynamics, tensegrity structures pose a new set of problems, i.e., initial shape finding. Initial configurations of tensegrity structures must be computed by imposing a pre-stressability condition to initial equilibrium equations. There are ample qualitative statements regarding the initial geometry of cylindrical and spherical tensegrity modules. Quantitative initial shape anlyses have only been performed on one-stage and two-stage cylindrical modules. However, analytical expressions for important geometrical parameters such as twist angles and overlap ratios lack the definition of the initial shape of both cylindrical and spherical tensegrity modules. In response to the above needs, a set of static and dynamic characterization procedures for tensegrity modules was first developed. The procedures were subsequently applied to Buckminster Fuller's spherical tensegrity modules. Both the initial shape and the corresponding pre-stress mode were analytically obtained by using the graphs of the tetrahedral, octahedral (cubic), and icosahedral (dodecahedral) groups. For pre-stressed configurations, modal analyses were conducted to classify a large number of infinitesimal mechanism modes. The procedures also applied tocyclic cylindrical tensegrity modules with an arbitrary number of stages. It was found that both the Maxwell number and the number of infinitesimal mechanism modes are independent of the number of stages in the axial direction. A reduced set of equilibrium equations was derived by incorporating cyclic symmetry and the flip, or quasi-flip, symmetry of the cylindrical modules. For multi-stage modules with more than

  12. Signal Transduction Pathways of TNAP: Molecular Network Analyses.

    PubMed

    Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp

    2015-01-01

    Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

  13. Time-frequency Analyses of AE Signals in YBCO Superconductors

    NASA Astrophysics Data System (ADS)

    Nanato, N.; Takemoto, N.

    AE (Acoustic Emission) measurements are well known methods to detect mechanical signals from superconducting coil The mechanical signals could be generated by micro cracks of epoxy resins, the motion of superconductors and the thermal expansion of superconductors, which were generated before and/or after a quench. We have presented a time-frequency visualization of AE signals as a method to detect the quench. We can detect very small AE signals regardless of lectromagnetic noises and can find the time of the AE occurrence and the frequency bands of AE signals by using this method. Recently it has been presented that YBCO superconductors are delaminated and degraded by a transverse tensile stress. The delamination is accompanied with AE signals. Also, it is known that amplitudes and frequency bands of AE signals vary with causes of AE occurrence. In this paper, we present time-frequency analyses of AE signa s caused by the delamination of a YBCO superconductor and the micro of epoxy resins.

  14. Comparative analyses of lysophosphatidic acid receptor-mediated signaling.

    PubMed

    Fukushima, Nobuyuki; Ishii, Shoichi; Tsujiuchi, Toshifumi; Kagawa, Nao; Katoh, Kazutaka

    2015-06-01

    Lysophosphatidic acid (LPA) is a bioactive lipid mediator that activates G protein-coupled LPA receptors to exert fundamental cellular functions. Six LPA receptor genes have been identified in vertebrates and are classified into two subfamilies, the endothelial differentiation genes (edg) and the non-edg family. Studies using genetically engineered mice, frogs, and zebrafish have demonstrated that LPA receptor-mediated signaling has biological, developmental, and pathophysiological functions. Computational analyses have also identified several amino acids (aa) critical for LPA recognition by human LPA receptors. This review focuses on the evolutionary aspects of LPA receptor-mediated signaling by comparing the aa sequences of vertebrate LPA receptors and LPA-producing enzymes; it also summarizes the LPA receptor-dependent effects commonly observed in mouse, frog, and fish.

  15. Universal signal generator for dynamic cell stimulation.

    PubMed

    Piehler, Andreas; Ghorashian, Navid; Zhang, Ce; Tay, Savaş

    2017-06-27

    Dynamic cell stimulation is a powerful technique for probing gene networks and for applications in stem cell differentiation, immunomodulation and signaling. We developed a robust and flexible method and associated microfluidic devices to generate a wide-range of precisely formulated dynamic chemical signals to stimulate live cells and measure their dynamic response. This signal generator is capable of digital to analog conversion (DAC) through combinatoric selection of discrete input concentrations, and outperforms existing methods by both achievable resolution, dynamic range and simplicity in design. It requires no calibration, has minimal space requirements and can be easily integrated into microfluidic cell culture devices. The signal generator hardware and software we developed allows to choose the waveform, period and amplitude of chemical input signals and features addition of well-defined chemical noise to study the role of stochasticity in cellular information processing.

  16. Dynamic Analyses Including Joints Of Truss Structures

    NASA Technical Reports Server (NTRS)

    Belvin, W. Keith

    1991-01-01

    Method for mathematically modeling joints to assess influences of joints on dynamic response of truss structures developed in study. Only structures with low-frequency oscillations considered; only Coulomb friction and viscous damping included in analysis. Focus of effort to obtain finite-element mathematical models of joints exhibiting load-vs.-deflection behavior similar to measured load-vs.-deflection behavior of real joints. Experiments performed to determine stiffness and damping nonlinearities typical of joint hardware. Algorithm for computing coefficients of analytical joint models based on test data developed to enable study of linear and nonlinear effects of joints on global structural response. Besides intended application to large space structures, applications in nonaerospace community include ground-based antennas and earthquake-resistant steel-framed buildings.

  17. Analyses and Measures of GPR Signal with Superimposed Noise

    NASA Astrophysics Data System (ADS)

    Chicarella, Simone; Ferrara, Vincenzo; D'Atanasio, Paolo; Frezza, Fabrizio; Pajewski, Lara; Pavoncello, Settimio; Prontera, Santo; Tedeschi, Nicola; Zambotti, Alessandro

    2014-05-01

    The influence of EM noises and environmental hard conditions on the GPR surveys has been examined analytically [1]. In the case of pulse radar GPR, many unwanted signals as stationary clutter, non-stationary clutter, random noise, and time jitter, influence the measurement signal. When GPR is motionless, stationary clutter is the most dominant signal component due to the reflections of static objects different from the investigated target, and to the direct antenna coupling. Moving objects like e.g. persons and vehicles, and the swaying of tree crown, produce non-stationary clutter. Device internal noise and narrowband jamming are e.g. two potential sources of random noises. Finally, trigger instabilities generate random jitter. In order to estimate the effective influence of these noise signal components, we organized some experimental setup of measurement. At first, we evaluated for the case of a GPR basic detection, simpler image processing of radargram. In the future, we foresee experimental measurements for detection of the Doppler frequency changes induced by movements of targets (like physiological movements of survivors under debris). We obtain image processing of radargram by using of GSSI SIR® 2000 GPR system together with the UWB UHF GPR-antenna (SUB-ECHO HBD 300, a model manufactured by Radarteam company). Our work includes both characterization of GPR signal without (or almost without) a superimposed noise, and the effect of jamming originated from the coexistence of a different radio signal. For characterizing GPR signal, we organized a measurement setup that includes the following instruments: mod. FSP 30 spectrum analyser by Rohde & Schwarz which operates in the frequency range 9 KHz - 30 GHz, mod. Sucoflex 104 cable by Huber Suhner (10 MHz - 18 GHz), and HL050 antenna by Rohde & Schwarz (bandwidth: from 850 MHz to 26.5 GHz). The next analysis of superimposed jamming will examine two different signal sources: by a cellular phone and by a

  18. Two complementary paradigms for analysing population dynamics.

    PubMed Central

    Krebs, Charles J

    2002-01-01

    To understand why population growth rate is sometimes positive and sometimes negative, ecologists have adopted two main approaches. The most common approach is through the density paradigm by plotting population growth rate against population density. The second approach is through the mechanistic paradigm by plotting population growth rate against the relevant ecological processes affecting the population. The density paradigm is applied a posteriori, works sometimes but not always and is remarkably useless in solving management problems or in providing an understanding of why populations change in size. The mechanistic paradigm investigates the factors that supposedly drive density changes and is identical to Caughley's declining population paradigm of conservation biology. The assumption that we can uncover invariant relationships between population growth rate and some other variables is an article of faith. Numerous commercial fishery applications have failed to find the invariant relationships between stock and recruitment that are predicted by the density paradigm. Environmental variation is the rule, and non-equilibrial dynamics should force us to look for the mechanisms of population change. If multiple factors determine changes in population density, there can be no predictability in either of these paradigms and we will become environmental historians rather than scientists with useful generalizations for the population problems of this century. Defining our questions clearly and adopting an experimental approach with crisp alternative hypotheses and adequate controls will be essential to building useful generalizations for solving the practical problems of population management in fisheries, wildlife and conservation. PMID:12396513

  19. Dynamic decomposition of spatiotemporal neural signals

    PubMed Central

    2017-01-01

    Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks. Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing. Here we present a data analysis framework that uses a linearized model of these dynamic states in order to decompose the measured neural signal into a series of components that capture both rhythmic and non-rhythmic neural activity. The method is based on stochastic differential equations and Gaussian process regression. Through computer simulations and analysis of magnetoencephalographic data, we demonstrate the efficacy of the method in identifying meaningful modulations of oscillatory signals corrupted by structured temporal and spatiotemporal noise. These results suggest that the method is particularly suitable for the analysis and interpretation of complex temporal and spatiotemporal neural signals. PMID:28558039

  20. Analytical signal analysis of strange nonchaotic dynamics.

    PubMed

    Gupta, Kopal; Prasad, Awadhesh; Singh, Harinder P; Ramaswamy, Ramakrishna

    2008-04-01

    We apply an analytical signal analysis to strange nonchaotic dynamics. Through this technique it is possible to obtain the spectrum of instantaneous intrinsic mode frequencies that are present in a given signal. We find that the second-mode frequency and its variance are good order parameters for dynamical transitions from quasiperiodic tori to strange nonchaotic attractors (SNAs) and from SNAs to chaotic attractors. Phase fluctuation analysis shows that SNAs and chaotic attractors behave identically within short time windows as a consequence of local instabilities in the dynamics. In longer time windows, however, the globally stable character of SNAs becomes apparent. This methodology can be of great utility in the analysis of experimental time series, and representative applications are made to signals obtained from Rössler and Duffing oscillators.

  1. Dynamic Redox Regulation of IL-4 Signaling

    PubMed Central

    Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

    2015-01-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  2. Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway

    PubMed Central

    Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar

    2014-01-01

    Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232

  3. Software for analysing multifocal visual evoked potential signal latency progression.

    PubMed

    de Santiago, L; Klistorner, A; Ortiz, M; Fernández-Rodríguez, A J; Rodríguez Ascariz, J M; Barea, R; Miguel-Jiménez, J M; Boquete, L

    2015-04-01

    This paper describes a new non-commercial software application (mfVEP(2)) developed to process multifocal visual-evoked-potential (mfVEP) signals in latency (monocular and interocular) progression studies. The software performs analysis by cross-correlating signals from the same patients. The criteria applied by the software include best channels, signal window, cross-correlation limits and signal-to-noise ratio (SNR). Software features include signal display comparing different tests and groups of sectors (quadrants, rings and hemispheres). The software's performance and capabilities are demonstrated on the results obtained from a patient with acute optic neuritis who underwent 9 follow-up mfVEP tests. Numerical values and graphics are presented and discussed for this case. The authors present a software application used to study progression in mfVEP signals. It is also useful in research projects designed to improve mfVEP techniques. This software makes it easier for users to manage the signals and allows them to choose various ways of selecting signals and representing results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Microwave signal processing with photorefractive dynamic holography

    NASA Astrophysics Data System (ADS)

    Fotheringham, Edeline B.

    Have you ever found yourself listening to the music playing from the closest stereo rather than to the bromidic (uninspiring) person speaking to you? Your ears receive information from two sources but your brain listens to only one. What if your cell phone could distinguish among signals sharing the same bandwidth too? There would be no "full" channels to stop you from placing or receiving a call. This thesis presents a nonlinear optical circuit capable of distinguishing uncorrelated signals that have overlapping temporal bandwidths. This so called autotuning filter is the size of a U.S. quarter dollar and requires less than 3 mW of optical power to operate. It is basically an oscillator in which the losses are compensated with dynamic holographic gain. The combination of two photorefractive crystals in the resonator governs the filter's winner-take-all dynamics through signal-competition for gain. This physical circuit extracts what is mathematically referred to as the largest principal component of its spatio-temporal input space. The circuit's practicality is demonstrated by its incorporation in an RF-photonic system. An unknown mixture of unknown microwave signals, received by an antenna array, constitutes the input to the system. The output electronically returns one of the original microwave signals. The front-end of the system down converts the 10 GHz microwave signals and amplifies them before the signals phase modulate optical beams. The optical carrier is suppressed from these beams so that it may not be considered as a signal itself to the autotuning filter. The suppression is achieved with two-beam coupling in a single photorefractive crystal. The filter extracts the more intense of the signals present on the carrier-suppressed input beams. The detection of the extracted signal restores the microwave signal to an electronic form. The system, without the receiving antenna array, is packaged in a 13 x 18 x 6″ briefcase. Its power consumption equals that

  5. Pattern Selection by Dynamical Biochemical Signals

    PubMed Central

    Palau-Ortin, David; Formosa-Jordan, Pau; Sancho, José M.; Ibañes, Marta

    2015-01-01

    The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell

  6. Decoding dynamic Ca2+ signaling in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael

    2014-01-01

    Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis. PMID:25452732

  7. Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites.

    PubMed

    Macocinschi, Doina; Filip, Daniela; Vlad, Stelian; Cristea, Mariana; Musteata, Valentina; Ibanescu, Sorin

    2012-08-01

    Polymer biocomposites based on segmented poly(ester urethane) and extracellular matrix components have been prepared for the development of tissue engineering applications with improved biological characteristics of the materials in contact with blood and tissues for long periods. Thermal, dynamical, and dielectrical analyses were employed to study the molecular dynamics of these materials and the influence of changing the physical network morphology and hydrogen bond interactions accompanied by phase transitions, interfacial effects, and polarization or conductivity. All phenomena that concur in the tested materials are evaluated by cross-examination of the dynamic mechanical characteristic properties (storage modulus, loss modulus, and loss factor) and dielectric properties (relative permittivity, relative loss factor, and loss tangent) as a function of temperature. Comparative aspects were elucidated by calculating the apparent activation energies of multiplex experiments.

  8. Preliminary Analyses of Beidou Signal-In Anomaly Since 2013

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Ren, J.; Liu, W.

    2016-06-01

    As BeiDou navigation system has been operational since December 2012. There is an increasing desire to use multiple constellation to improve positioning performance. The signal-in-space (SIS) anomaly caused by the ground control and the space vehicle is one of the major threats to affect the integrity. For a young Global Navigation Satellite System, knowledge about SIS anomalies in history is very important for not only assessing the SIS integrity performance of a constellation but also providing the assumption for ARAIM (Advanced Receiver Autonomous Integrity Monitoring). In this paper, the broadcast ephemerides and the precise ones are pre-processed for avoiding the false anomaly identification. The SIS errors over the period of Mar. 2013-Feb. 2016 are computed by comparing the broadcast ephemerides with the precise ones. The time offsets between GPST (GPS time) and BDT (BeiDou time) are estimated and removed by an improved estimation algorithm. SIS worst-UREs are computed and a RMS criteria are investigated to identify the SIS anomalies. The results show that the probability of BeiDou SIS anomalies is in 10-3 level in last three years. Even though BeiDou SIS integrity performance currently cannot match the GPS integrity performances, the result indicates that BeiDou has a tendency to improve its integrity performance.

  9. Noise reduction by dynamic signal preemphasis

    NASA Astrophysics Data System (ADS)

    Takeda, Kazuyuki; Takegoshi, K.

    2011-02-01

    In this work we propose an approach to reduce the digitization noise for a given dynamic range, i.e., the number of bits, of an analog to digital converter used in an NMR receiver. In this approach, the receiver gain is dynamically increased so that the free induction decay is recorded in such an emphasized way that the decaying signal is digitized using as many number of bits as possible, and at the stage of data processing, the original signal profile is restored by applying the apodization that compensates the effect of the preemphasis. This approach, which we call APodization after Receiver gain InCrement during Ongoing sequence with Time (APRICOT), is performed in a solid-state system containing a pair of 13C spins, one of which is fully isotopically labeled and the other is naturally abundant. It is demonstrated that the exceedingly smaller peak buried in the digitization noise in the conventional approach can be revealed by employing APRICOT.

  10. Noise reduction by dynamic signal preemphasis.

    PubMed

    Takeda, Kazuyuki; Takegoshi, K

    2011-02-01

    In this work we propose an approach to reduce the digitization noise for a given dynamic range, i.e., the number of bits, of an analog to digital converter used in an NMR receiver. In this approach, the receiver gain is dynamically increased so that the free induction decay is recorded in such an emphasized way that the decaying signal is digitized using as many number of bits as possible, and at the stage of data processing, the original signal profile is restored by applying the apodization that compensates the effect of the preemphasis. This approach, which we call APodization after Receiver gain InCrement during Ongoing sequence with Time (APRICOT), is performed in a solid-state system containing a pair of (13)C spins, one of which is fully isotopically labeled and the other is naturally abundant. It is demonstrated that the exceedingly smaller peak buried in the digitization noise in the conventional approach can be revealed by employing APRICOT. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Perspective: Dynamics of receptor tyrosine kinase signaling complexes.

    PubMed

    Mayer, Bruce J

    2012-08-14

    Textbook descriptions of signal transduction complexes provide a static snapshot view of highly dynamic events. Despite enormous strides in identifying the key components of signaling complexes and the underlying mechanisms of signal transduction, our understanding of the dynamic behavior of these complexes has lagged behind. Using the example of receptor tyrosine kinases, this perspective takes a fresh look at the dynamics of the system and their potential impact on signal processing.

  12. Plant phosphoinositide signaling - dynamics on demand.

    PubMed

    Heilmann, Ingo

    2016-09-01

    Eukaryotic membranes contain small amounts of lipids with regulatory roles. An important class of such regulatory lipids are phosphoinositides (PIs). Within membranes, PIs serve as recruitment signals, as regulators of membrane protein function or as precursors for second messenger production, thereby influencing a multitude of cellular processes with key importance for plant function and development. Plant PIs occur locally and transiently within membrane microdomains, and their abundance is strictly controlled. To understand the functions of the plant PI-network it is important to understand not only downstream PI-effects, but also to identify and characterize factors contributing to dynamic PI formation. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Analysing connectivity with Granger causality and dynamic causal modelling.

    PubMed

    Friston, Karl; Moran, Rosalyn; Seth, Anil K

    2013-04-01

    This review considers state-of-the-art analyses of functional integration in neuronal macrocircuits. We focus on detecting and estimating directed connectivity in neuronal networks using Granger causality (GC) and dynamic causal modelling (DCM). These approaches are considered in the context of functional segregation and integration and--within functional integration--the distinction between functional and effective connectivity. We review recent developments that have enjoyed a rapid uptake in the discovery and quantification of functional brain architectures. GC and DCM have distinct and complementary ambitions that are usefully considered in relation to the detection of functional connectivity and the identification of models of effective connectivity. We highlight the basic ideas upon which they are grounded, provide a comparative evaluation and point to some outstanding issues.

  14. Strength and dynamic characteristics analyses of wound composite axial impeller

    NASA Astrophysics Data System (ADS)

    Wang, Jifeng; Olortegui-Yume, Jorge; Müller, Norbert

    2012-03-01

    A low cost, light weight, high performance composite material turbomachinery impeller with a uniquely designed blade patterns is analyzed. Such impellers can economically enable refrigeration plants to use water as a refrigerant (R718). A strength and dynamic characteristics analyses procedure is developed to assess the maximum stresses and natural frequencies of these wound composite axial impellers under operating loading conditions. Numerical simulation using FEM for two-dimensional and three-dimensional impellers was investigated. A commercially available software ANSYS is used for the finite element calculations. Analysis is done for different blade geometries and then suggestions are made for optimum design parameters. In order to avoid operating at resonance, which can make impellers suffer a significant reduction in the design life, the designer must calculate the natural frequency and modal shape of the impeller to analyze the dynamic characteristics. The results show that using composite Kevlar fiber/epoxy matrix enables the impeller to run at high tip speed and withstand the stresses, no critical speed will be matched during start-up and shut-down, and that mass imbalances of the impeller shall not pose a critical problem.

  15. Space station static and dynamic analyses using parallel methods

    NASA Technical Reports Server (NTRS)

    Gupta, V.; Newell, J.; Storaasli, O.; Baddourah, M.; Bostic, S.

    1993-01-01

    Algorithms for high-performance parallel computers are applied to perform static analyses of large-scale Space Station finite-element models (FEMs). Several parallel-vector algorithms under development at NASA Langley are assessed. Sparse matrix solvers were found to be more efficient than banded symmetric or iterative solvers for the static analysis of large-scale applications. In addition, new sparse and 'out-of-core' solvers were found superior to substructure (superelement) techniques which require significant additional cost and time to perform static condensation during global FEM matrix generation as well as the subsequent recovery and expansion. A method to extend the fast parallel static solution techniques to reduce the computation time for dynamic analysis is also described. The resulting static and dynamic algorithms offer design economy for preliminary multidisciplinary design optimization and FEM validation against test modes. The algorithms are being optimized for parallel computers to solve one-million degrees-of-freedom (DOF) FEMs. The high-performance computers at NASA afforded effective software development, testing, efficient and accurate solution with timely system response and graphical interpretation of results rarely found in industry. Based on the author's experience, similar cooperation between industry and government should be encouraged for similar large-scale projects in the future.

  16. Space station static and dynamic analyses using parallel methods

    NASA Technical Reports Server (NTRS)

    Gupta, V.; Newell, J.; Storaasli, O.; Baddourah, M.; Bostic, S.

    1993-01-01

    Algorithms for high-performance parallel computers are applied to perform static analyses of large-scale Space Station finite-element models (FEMs). Several parallel-vector algorithms under development at NASA Langley are assessed. Sparse matrix solvers were found to be more efficient than banded symmetric or iterative solvers for the static analysis of large-scale applications. In addition, new sparse and 'out-of-core' solvers were found superior to substructure (superelement) techniques which require significant additional cost and time to perform static condensation during global FEM matrix generation as well as the subsequent recovery and expansion. A method to extend the fast parallel static solution techniques to reduce the computation time for dynamic analysis is also described. The resulting static and dynamic algorithms offer design economy for preliminary multidisciplinary design optimization and FEM validation against test modes. The algorithms are being optimized for parallel computers to solve one-million degrees-of-freedom (DOF) FEMs. The high-performance computers at NASA afforded effective software development, testing, efficient and accurate solution with timely system response and graphical interpretation of results rarely found in industry. Based on the author's experience, similar cooperation between industry and government should be encouraged for similar large-scale projects in the future.

  17. Dynamic ubiquitin signaling in cell cycle regulation.

    PubMed

    Gilberto, Samuel; Peter, Matthias

    2017-08-07

    The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

  18. [Dynamic Pulse Signal Processing and Analyzing in Mobile System].

    PubMed

    Chou, Yongxin; Zhang, Aihua; Ou, Jiqing; Qi, Yusheng

    2015-09-01

    In order to derive dynamic pulse rate variability (DPRV) signal from dynamic pulse signal in real time, a method for extracting DPRV signal was proposed and a portable mobile monitoring system was designed. The system consists of a front end for collecting and wireless sending pulse signal and a mobile terminal. The proposed method is employed to extract DPRV from dynamic pulse signal in mobile terminal, and the DPRV signal is analyzed both in the time domain and the frequency domain and also with non-linear method in real time. The results show that the proposed method can accurately derive DPRV signal in real time, the system can be used for processing and analyzing DPRV signal in real time.

  19. Dynamical Analyses for Developmental Science: A Primer for Intrigued Scientists

    ERIC Educational Resources Information Center

    DiDonato, M. D.; England, D.; Martin, C. L.; Amazeen, P. G.

    2013-01-01

    Dynamical systems theory is becoming more popular in social and developmental science. However, unfamiliarity with dynamical analysis techniques remains an obstacle for developmentalists who would like to quantitatively apply dynamics in their own research. The goal of this article is to address this issue by clearly and simply presenting several…

  20. Dynamical Analyses for Developmental Science: A Primer for Intrigued Scientists

    ERIC Educational Resources Information Center

    DiDonato, M. D.; England, D.; Martin, C. L.; Amazeen, P. G.

    2013-01-01

    Dynamical systems theory is becoming more popular in social and developmental science. However, unfamiliarity with dynamical analysis techniques remains an obstacle for developmentalists who would like to quantitatively apply dynamics in their own research. The goal of this article is to address this issue by clearly and simply presenting several…

  1. Methods of dynamic spectral analysis by self-exciting autoregressive moving average models and their application to analysing biosignals.

    PubMed

    Schack, B; Bareshova, E; Grieszbach, G; Witte, H

    1995-05-01

    Dynamic methods in the spectral domain are necessary to analyse biological signals because of the frequently nonstationary character of the signals. The paper presents an adaptive procedure of fitting time-dependent ARMA models to nonstationary signals, which is suitable for on-line calculations. The properties of the model parameter estimations are examined, and in the stationary case are compared with the results of convergent estimation methods. On this basis time-varying spectral parameters with high temporal and spectral resolution are calculated, and the possibility of their application is shown in EEG analysis and laser-Doppler-flowmetry.

  2. Bias Analyses of Preclinical and Clinical D2 Dopamine Ligands: Studies with Immediate and Complex Signaling Pathways

    PubMed Central

    Brust, Tarsis F.; Hayes, Michael P.; Roman, David L.; Burris, Kevin D.

    2015-01-01

    G protein–coupled receptors (GPCRs) often activate multiple signaling pathways, and ligands may evoke functional responses through individual pathways. These unique responses provide opportunities for biased or functionally selective ligands to preferentially modulate one signaling pathway over another. Studies with several GPCRs have suggested that selective activation of signaling pathways downstream of a GPCR may lead to safer and more effective drug therapies. The dopamine D2 receptor (D2R) is one of the main drug targets in the therapies for Parkinson’s disease and schizophrenia. Recent studies suggest that selective modulation of individual signaling pathways downstream of the D2R may lead to safer antipsychotic drugs. In the present study, immediate effectors of the D2R (i.e., Gαi/o, Gβγ, β-arrestin recruitment) and more complex signaling pathways (i.e., extracellular signal-regulated kinase phosphorylation, heterologous sensitization, and dynamic mass redistribution) were examined in response to a series of D2R ligands. This was accomplished using Chinese hamster ovary cells stably expressing the human D2L dopamine receptor in the PathHunter β-Arrestin GPCR Assay Platform. The use of a uniform cellular background was designed to eliminate potential confounds associated with cell-to-cell variability, including expression levels of receptor as well as other components of signal transduction, including G protein subunits. Several well characterized and clinically relevant D2R ligands were evaluated across each signaling pathway in this cellular model. The most commonly used methods to measure ligand bias were compared. Functional selectivity analyses were also used as tools to explore the relative contribution of immediate D2R effectors for the activation of more complex signaling pathways. PMID:25539635

  3. A dynamical model for generating synthetic Phonocardiogram signals

    PubMed Central

    Almasi, Ali; Shamsollahi, Mohammad-Bagher; Senhadji, Lotfi

    2011-01-01

    In this paper we introduce a dynamical model for Phonocardiogram (PCG) signal which is capable of generating realistic synthetic PCG signals. This model is based on PCG morphology and consists of three ordinary differential equations and can represent various morphologies of normal PCG signals. Beat-to-beat variation in PCG morphology is significant so model parameters vary from beat to beat. This model is inspired of Electrocardiogram (ECG) dynamical model proposed by McSharry et al. and can be employed to assess biomedical signal processing techniques. PMID:22255630

  4. Chaotic Ising-like dynamics in traffic signals

    PubMed Central

    Suzuki, Hideyuki; Imura, Jun-ichi; Aihara, Kazuyuki

    2013-01-01

    The green and red lights of a traffic signal can be viewed as the up and down states of an Ising spin. Moreover, traffic signals in a city interact with each other, if they are controlled in a decentralised way. In this paper, a simple model of such interacting signals on a finite-size two-dimensional lattice is shown to have Ising-like dynamics that undergoes a ferromagnetic phase transition. Probabilistic behaviour of the model is realised by chaotic billiard dynamics that arises from coupled non-chaotic elements. This purely deterministic model is expected to serve as a starting point for considering statistical mechanics of traffic signals. PMID:23350034

  5. Marginal Utility of Conditional Sensitivity Analyses for Dynamic Models

    EPA Science Inventory

    Background/Question/MethodsDynamic ecological processes may be influenced by many factors. Simulation models thatmimic these processes often have complex implementations with many parameters. Sensitivityanalyses are subsequently used to identify critical parameters whose uncertai...

  6. Marginal Utility of Conditional Sensitivity Analyses for Dynamic Models

    EPA Science Inventory

    Background/Question/MethodsDynamic ecological processes may be influenced by many factors. Simulation models thatmimic these processes often have complex implementations with many parameters. Sensitivityanalyses are subsequently used to identify critical parameters whose uncertai...

  7. Temporal and Evolutionary Dynamics of Two-Component Signaling Pathways

    PubMed Central

    Salazar, Michael E.; Laub, Michael T.

    2015-01-01

    Bacteria sense and respond to numerous environmental signals through two-component signaling pathways. Typically, a given stimulus will activate a sensor histidine kinase to autophosphorylate and then phosphotransfer to a cognate response regulator, which can mount an appropriate response. Although these signaling pathways often appear to be simple switches, they can also orchestrate surprisingly sophisticated and complex responses. These temporal dynamics arise from several key regulatory features, including the bifunctionality of histidine kinases as well as positive and negative feedback loops. Two-component signaling pathways are also dynamic on evolutionary time-scales, expanding dramatically in many species through gene duplication and divergence. Here, we review recent work probing the temporal and evolutionary dynamics of two-component signaling systems. PMID:25589045

  8. Dynamics of a sensory signaling network in a unicellular eukaryote.

    PubMed

    Foster, Kenneth W; Josef, Keith; Saranak, Jureepan; Tuck, Ned

    2006-01-01

    The processing components and the dynamic signaling network that an individual cell uses to do signal integration and make decisions based on multiple sensory inputs are being identified in a well studied free-swimming unicellular green algal model organism, Chlamydomonas. It has many sensory photoreceptors and measurable behavior associated with its orienting and swimming with respect to light sources in its environment. Study of the dynamics of the beating of its two steering cilia reveals their complex specialization.

  9. Summary of dynamic analyses of selected NSS buildings. Final report

    SciTech Connect

    Beck, J.E.

    1980-07-01

    This report covers the collapse analyses of floor-over-basement areas. The floors were separated into floor systems and were analyzed 'as built' and for various upgrading configurations through an examination of individual elements. The purpose of the report is two-fold: first, to increase the data base of analyzed 'as built' NSS building floors; and second, to determine the expedient upgrading potentials of NSS building floors. This report summarizes the results of the collapse analyses of the 11 NSS buildings examined in this study. The results of the 'as built' analyses are then grouped with the collapse analyses of 36 NSS buildings to provide a population of 46 buildings (one building was reexamined). The predicted collapse overpressures, examined previously by Wiehle (1974), of the weakest floor element by building and by floor system are presented in the form of histograms and cumulative frequency distributions. The effect of frame type on the collapse strength of the floor elements was examined as in the previous report (Wiehle, 1974). This report also summarizes, for the 11 buildings analyzed herein, the upgrading potentials of floor elements grouped by individual element, floor system and building. Preliminary indications of these collapse analyses indicate that the best way to assess which building and/or element is most upgradable is to look for elements, especially slabs or pan-joist systems, having the greatest span.

  10. Dynamic analyses of viscoelastic dielectric elastomers incorporating viscous damping effect

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Zhao, Jianwen; Chen, Hualing; Li, Dichen

    2017-01-01

    In this paper, based on the standard linear solid rheological model, a dynamics model of viscoelastic dielectric elastomers (DEs) is developed with incorporation of viscous damping effect. Numerical calculations are employed to predict the damping effect on the dynamic performance of DEs. With increase of damping force, the DEs show weak nonlinearity and vibration strength. Phase diagrams and Poincaré maps are utilized to detect the dynamic stability of DEs, and the results indicate that a transition from aperiodic vibration to quasi-periodic vibration occurs with enlargement of damping force. The resonance properties of DEs including damping effect are subsequently analyzed, demonstrating a reduction of resonant frequency and resonance peak with increase of damping force.

  11. Analysis of insulin receptor substrate signaling dynamics on microstructured surfaces.

    PubMed

    Lanzerstorfer, Peter; Yoneyama, Yosuke; Hakuno, Fumihiko; Müller, Ulrike; Höglinger, Otmar; Takahashi, Shin-Ichiro; Weghuber, Julian

    2015-03-01

    Insulin receptor substrates (IRS) are phosphorylated by activated insulin/insulin-like growth factor I receptor tyrosine kinases, with this comprising an initial key event for downstream signaling and bioactivities. Despite the structural similarities, increasing evidence shows that IRS family proteins have nonredundant functions. Although the specificity of insulin/insulin-like growth factor signaling and biological responses partly reflects which IRS proteins are dominantly phosphorylated by the receptors, the precise properties of the respective IRS interaction with the receptors remain elusive. In the present study, we utilized a technique that combines micropatterned surfaces and total internal reflection fluorescence microscopy for the quantitative analysis of the interaction between IRS proteins and insulin/insulin-like growth factor in living cells. Our experimental set-up enabled the measurement of equilibrium associations and interaction dynamics of these molecules with high specificity. We revealed that several domains of IRS including pleckstrin homology and phosphotyrosine binding domains critically determine the turnover rate of the receptors. Furthermore, we found significant differences among IRS proteins in the strength and kinetic stability of the interaction with the receptors, suggesting that these interaction properties could account for the diverse functions of IRS. In addition, our analyses using fluorescent recovery after photobleaching revealed that kinases such as c-Jun N-terminal kinase and IκB kinase β, which phosphorylate serine/threonine residues of IRS and contribute to insulin resistance, altered the interaction kinetics of IRS with insulin receptor. Collectively, our experimental set-up is a valuable system for quantitifying the physiological interaction of IRS with the receptors in insulin/insulin-like growth factor signaling. © 2015 FEBS.

  12. Dynamic Programming Algorithms and Analyses for Nonserial Networks. Part I.

    DTIC Science & Technology

    1983-01-01

    Journal of Mathematical Analysis and Applications , Vol...Multistage Systems," Journal of Mathematical Analysis and Applications , Vol. 21, 1968, pp. 426-430. 4. Bellman, R.E.,A.O. Esogbue, and I. Nabeshima...the Secondary Optimization Problem in Nonserial Dynamic Programming," Journal of Mathematical Analysis and Applications , Vol. 27, 1969, pp. 565-574.

  13. The dynamic mechanism of noisy signal decoding in gene regulation

    PubMed Central

    Liu, Peijiang; Wang, Haohua; Huang, Lifang; Zhou, Tianshou

    2017-01-01

    Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation. In addition, we find that the input noise can induce stochastic focusing in a regulation-dependent manner. These results reveal not only the dynamic mechanism of noisy signal decoding in gene regulation but also the essential role of external noise in controlling gene expression levels. PMID:28176840

  14. The dynamic mechanism of noisy signal decoding in gene regulation.

    PubMed

    Liu, Peijiang; Wang, Haohua; Huang, Lifang; Zhou, Tianshou

    2017-02-08

    Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation. In addition, we find that the input noise can induce stochastic focusing in a regulation-dependent manner. These results reveal not only the dynamic mechanism of noisy signal decoding in gene regulation but also the essential role of external noise in controlling gene expression levels.

  15. Dynamical collective calculation of supernova neutrino signals.

    PubMed

    Gava, Jérôme; Kneller, James; Volpe, Cristina; McLaughlin, G C

    2009-08-14

    We present the first calculations with three flavors of collective and shock wave effects for neutrino propagation in core-collapse supernovae using hydrodynamical density profiles and the S matrix formalism. We explore the interplay between the neutrino-neutrino interaction and the effects of multiple resonances upon the time signal of positrons in supernova observatories. A specific signature is found for the inverted hierarchy and a large third neutrino mixing angle and we predict, in this case, a dearth of lower energy positrons in Cherenkov detectors midway through the neutrino signal and the simultaneous revelation of valuable information about the original fluxes. We show that this feature is also observable with current generation neutrino detectors at the level of several sigmas.

  16. Geophysical and fluid dynamical analyses in physical volcanology

    NASA Astrophysics Data System (ADS)

    Rogers, Patricia Grizzaffi

    Volcanism is a predominant process on the terrestrial planets, and studies of physical volcanologic processes provide fundamental insight into the evolution of a planet's surface and interior. This work combines theoretical modeling, field observations, and studies of planetary surfaces in an integrated approach to understanding the mechanical and dynamic processes associated with volcanism. By understanding the basic dynamics associated with terrestrial volcanic processes, we hope to better understand the evolution of other planetary surfaces for which only remote sensing data are available. The focus of this work is the physics of volcanism in space and time, with an emphasis on regions that are dominated by volcanism such as the Hawaiian islands, and on studies of lava flow emplacement. Applying our knowledge of volcanic processes on Earth to studies of Venusian geology and geophysics is also important for this investigation because volcanism has been a primary process in creating and modifying landforms on that planet. This analysis of geophysical and fluid dynamic processes associated with physical volcanology first focuses on the relationship between volcanic and tectonic processes and the associated stress environments. Specifically, through analytical modeling we investigate the regional stresses associated with Bell Regio, a volcanic highland on Venus, and structural features believed to be a consequence of lithospheric flexure due to volcanic loading. The relationship between the tectonic features surrounding a volcanic edifice and stresses associated with magma chamber inflation are also examined through finite element analysis. The implications of a change in volcanic style and lithospheric thickness over time are discussed. Next, factors that affect the dynamics of lava flow emplacement are examined through a combination ot theoretical modeling and field measurements. Downflow changes in rheology and lava channel formation under conditions of varying

  17. Functional connectivity change as shared signal dynamics

    PubMed Central

    Cole, Michael W.; Yang, Genevieve J.; Murray, John D.; Repovš, Grega; Anticevic, Alan

    2015-01-01

    Background An increasing number of neuroscientific studies gain insights by focusing on differences in functional connectivity – between groups, individuals, temporal windows, or task conditions. We found using simulations that additional insights into such differences can be gained by forgoing variance normalization, a procedure used by most functional connectivity measures. Simulations indicated that these functional connectivity measures are sensitive to increases in independent fluctuations (unshared signal) in time series, consistently reducing functional connectivity estimates (e.g., correlations) even though such changes are unrelated to corresponding fluctuations (shared signal) between those time series. This is inconsistent with the common notion of functional connectivity as the amount of inter-region interaction. New Method Simulations revealed that a version of correlation without variance normalization – covariance – was able to isolate differences in shared signal, increasing interpretability of observed functional connectivity change. Simulations also revealed cases problematic for non-normalized methods, leading to a “covariance conjunction” method combining the benefits of both normalized and non-normalized approaches. Results We found that covariance and covariance conjunction methods can detect functional connectivity changes across a variety of tasks and rest in both clinical and non-clinical functional MRI datasets. Comparison with Existing Method(s) We verified using a variety of tasks and rest in both clinical and non-clinical functional MRI datasets that it matters in practice whether correlation, covariance, or covariance conjunction methods are used. Conclusions These results demonstrate the practical and theoretical utility of isolating changes in shared signal, improving the ability to interpret observed functional connectivity change. PMID:26642966

  18. Dynamic force signal processing system of a robot manipulator

    NASA Technical Reports Server (NTRS)

    Uchiyama, M.; Kitagaki, K.; Hakomori, K.

    1987-01-01

    If dynamic noises such as those caused by the inertia forces of the hand can be eliminated from the signal of the force sensor installed on the wrist of the robot manipulator and if the necessary information of the external force can be detected with high sensitivity and high accuracy, a fine force feedback control for robots used in high speed and various fields will be possible. As the dynamic force sensing system, an external force estimate method with the extended Kalman filter is suggested and simulations and tests for a one axis force were performed. Later a dynamic signal processing system of six axes was composed and tested. The results are presented.

  19. Analysing Dynamical Behavior of Cellular Networks via Stochastic Bifurcations

    PubMed Central

    Zakharova, Anna; Kurths, Jürgen; Vadivasova, Tatyana; Koseska, Aneta

    2011-01-01

    The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types. PMID:21647432

  20. Progressive alignment of genomic signals by multiple dynamic time warping.

    PubMed

    Skutkova, Helena; Vitek, Martin; Sedlar, Karel; Provaznik, Ivo

    2015-11-21

    This paper presents the utilization of progressive alignment principle for positional adjustment of a set of genomic signals with different lengths. The new method of multiple alignment of signals based on dynamic time warping is tested for the purpose of evaluating the similarity of different length genes in phylogenetic studies. Two sets of phylogenetic markers were used to demonstrate the effectiveness of the evaluation of intraspecies and interspecies genetic variability. The part of the proposed method is modification of pairwise alignment of two signals by dynamic time warping with using correlation in a sliding window. The correlation based dynamic time warping allows more accurate alignment dependent on local homologies in sequences without the need of scoring matrix or evolutionary models, because mutual similarities of residues are included in the numerical code of signals.

  1. Genetic and Dynamic Analyses of Murine Peak Bone Density

    DTIC Science & Technology

    1999-10-01

    4 vBMD loci shared with femurs (1, 4, 14, & 18) and 2 unique loci (Chr 7 & 9). Lastly, a new DEXA instrument for mice, the PIXhnus, has been...late 1999. The summarized results for the femoral total BMD analyses were: a) Genome wide scans for co-segregation of genetic marker data with high or...possible tools for drug discovery aimed at exogenous manipulation of bone density. New Instrumentation - PIXImus DEXA . We have been testing a dual energy

  2. Dynamic Vibrotactile Signals for Forward Collision Avoidance Warning Systems

    PubMed Central

    Meng, Fanxing; Gray, Rob; Ho, Cristy; Ahtamad, Mujthaba

    2015-01-01

    Objective: Four experiments were conducted in order to assess the effectiveness of dynamic vibrotactile collision-warning signals in potentially enhancing safe driving. Background: Auditory neuroscience research has demonstrated that auditory signals that move toward a person are more salient than those that move away. If this looming effect were found to extend to the tactile modality, then it could be utilized in the context of in-car warning signal design. Method: The effectiveness of various vibrotactile warning signals was assessed using a simulated car-following task. The vibrotactile warning signals consisted of dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity-toward-torso cues (Experiment 3), and static cues presented on the hands or on the waist, having either a low or high vibration intensity (Experiment 4). Results: Braking reaction times (BRTs) were significantly faster for toward-torso as compared to away-from-torso cues (Experiments 1 and 2) and static cues (Experiment 2). This difference could not have been attributed to differential responses to signals delivered to different body parts (i.e., the waist vs. hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso signal did not result in any additional BRT benefits (Experiment 3). Conclusion: Dynamic vibrotactile cues that feel as though they are approaching the torso can be used to communicate information concerning external events, resulting in a significantly faster reaction time to potential collisions. Application: Dynamic vibrotactile warning signals that move toward the body offer great potential for the design of future in-car collision-warning system. PMID:25850161

  3. Dynamic vibrotactile signals for forward collision avoidance warning systems.

    PubMed

    Meng, Fanxing; Gray, Rob; Ho, Cristy; Ahtamad, Mujthaba; Spence, Charles

    2015-03-01

    Four experiments were conducted in order to assess the effectiveness of dynamic vibrotactile collision-warning signals in potentially enhancing safe driving. Auditory neuroscience research has demonstrated that auditory signals that move toward a person are more salient than those that move away. If this looming effect were found to extend to the tactile modality, then it could be utilized in the context of in-car warning signal design. The effectiveness of various vibrotactile warning signals was assessed using a simulated car-following task. The vibrotactile warning signals consisted of dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity-toward-torso cues (Experiment 3), and static cues presented on the hands or on the waist, having either a low or high vibration intensity (Experiment 4). Braking reaction times (BRTs) were significantly faster for toward-torso as compared to away-from-torso cues (Experiments 1 and 2) and static cues (Experiment 2). This difference could not have been attributed to differential responses to signals delivered to different body parts (i.e., the waist vs. hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso signal did not result in any additional BRT benefits (Experiment 3). Dynamic vibrotactile cues that feel as though they are approaching the torso can be used to communicate information concerning external events, resulting in a significantly faster reaction time to potential collisions. Dynamic vibrotactile warning signals that move toward the body offer great potential for the design of future in-car collision-warning system. © 2014, Human Factors and Ergonomics Society.

  4. Dynamics of Mechanical Signal Transmission through Prestressed Stress Fibers

    PubMed Central

    Hwang, Yongyun; Barakat, Abdul I.

    2012-01-01

    Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows

  5. Coupled Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2000-01-01

    A procedure that models coupled thermo-mechanical deformations of viscoelastic rubber cylinders by employing the ABAQUS finite element code is described. Computational simulations of hysteretic heating are presented for several tall and short rubber cylinders both with and without a steel disk at their centers. The cylinders are compressed axially and are then cyclically loaded about the compressed state. The non-uniform hysteretic heating of the rubber cylinders containing a steel disk is presented. The analyses performed suggest that the coupling procedure should be considered for further development as a design tool for rubber degradation studies.

  6. Improved Aerodynamic Influence Coefficients for Dynamic Aeroelastic Analyses

    NASA Astrophysics Data System (ADS)

    Gratton, Patrice

    2011-12-01

    Currently at Bombardier Aerospace, aeroelastic analyses are performed using the Doublet Lattice Method (DLM) incorporated in the NASTRAN solver. This method proves to be very reliable and fast in preliminary design stages where wind tunnel experimental results are often not available. Unfortunately, the geometric simplifications and limitations of the DLM, based on the lifting surfaces theory, reduce the ability of this method to give reliable results for all flow conditions, particularly in transonic flow. Therefore, a new method has been developed involving aerodynamic data from high-fidelity CFD codes which solve the Euler or Navier-Stokes equations. These new aerodynamic loads are transmitted to the NASTRAN aeroelastic module through improved aerodynamic influence coefficients (AIC). A cantilevered wing model is created from the Global Express structural model and a set of natural modes is calculated for a baseline configuration of the structure. The baseline mode shapes are then combined with an interpolation scheme to deform the 3-D CFD mesh necessary for Euler and Navier-Stokes analyses. An uncoupled approach is preferred to allow aerodynamic information from different CFD codes. Following the steady state CFD analyses, pressure differences ( DeltaCp), calculated between the deformed models and the original geometry, lead to aerodynamic loads which are transferred to the DLM model. A modal-based AIC method is applied to the aerodynamic matrices of NASTRAN based on a least-square approximation to evaluate aerodynamic loads of a different wing configuration which displays similar types of mode shapes. The methodology developed in this research creates weighting factors based on steady CFD analyses which have an equivalent reduced frequency of zero. These factors are applied to both the real and imaginary part of the aerodynamic matrices as well as all reduced frequencies used in the PK-Method which solves flutter problems. The modal-based AIC method

  7. Dynamical states, possibilities and propagation of stress signal

    PubMed Central

    Malik, Md. Zubbair; Ali, Shahnawaz; Singh, Soibam Shyamchand; Ishrat, Romana; Singh, R. K. Brojen

    2017-01-01

    The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal. However, this stress system prefers to stay in an active dynamical state whose counterpart complex network is closest to hierarchical topology with exhibited roles of few interacting hubs. During the propagation of stress signal, the system allows the propagator pathway to inherit all possible properties of the state to the receiver pathway/pathways with slight modifications, indicating efficient information processing and democratic sharing of responsibilities in the system via cross-talk. The increase in the number of cross-talk pathways in the system favors to establish self-organization. PMID:28106087

  8. Dynamic and thermal analyses of flexible structures in orbit

    NASA Astrophysics Data System (ADS)

    Lin, Chijie

    Due to the launch cost and functional requirements, space structures, such as satellite antenna, deployable structures, solar sails, the space station, and solar panels, are necessarily built lightweight, large, and very flexible. These space structures undergo large orbital rigid body motions as well as large structural deformations caused by gravitational force and other disturbances, such as shuttle jet impingement loading, deployment factor, thermal effects, and debris impact. It is of utmost importance to study thoroughly the dynamic behavior of flexible structures in orbit under various external forces. In this study, first a finite element methodology program based on the absolute nodal coordinate formulation is developed to determine the coupled structural and orbital response of the flexible structure under gravitational and external loading, i.e., gravitational force, impact force, and jet impingement, and thermal loading. It is found from the simulation results that pitch and structural response of the flexible structures are greatly impacted by the initial and loading conditions, such as orbit eccentricity, initial misalignment, etc. The absolute nodal coordinate formulation may lead to inaccurate results due to the fact that the orbit radius is used for element coordinate, which is much greater than the amplitude of the pitch (attitude) motion and deformations of the orbiting structures. Therefore, to improve the accuracy of structural response in the simulation, a floating (moving) frame that is attached with the orbiting structure's center of mass and that moves parallel to the inertia frame fixed at the Earth's center is introduced to separate the attitude motion and structural deformation from the orbit radius. The finite element formulation is developed in this parallel reference frame system for two and three dimensional beam structures. It is then used to study dynamic response of flexible structures in two and three dimensional orbits. In some

  9. Information dynamics in cardiorespiratory analyses: application to controlled breathing.

    PubMed

    Widjaja, Devy; Faes, Luca; Montalto, Alessandro; Van Diest, Ilse; Marinazzo, Daniele; Van Huffel, Sabine

    2014-01-01

    Voluntary adjustment of the breathing pattern is widely used to deal with stress-related conditions. In this study, effects of slow and fast breathing with a low and high inspiratory to expiratory time on heart rate variability (HRV) are evaluated by means of information dynamics. Information transfer is quantified both as the traditional transfer entropy as well as the cross entropy, where the latter does not condition on the past of HRV, thereby taking the highly unidirectional relation between respiration and heart rate into account. The results show that the cross entropy is more suited to quantify cardiorespiratory information transfer as this measure increases during slow breathing, indicating the increased cardiorespiratory coupling and suggesting the shift towards vagal activation during slow breathing. Additionally we found that controlled breathing, either slow or fast, results as well in an increase in cardiorespiratory coupling, compared to spontaneous breathing, which demonstrates the beneficial effects of instructed breathing.

  10. Unsteady flow and dynamic response analyses for helicopter rotor blades

    NASA Technical Reports Server (NTRS)

    Bratanow, T.

    1979-01-01

    Research is presented on helicopter rotor blade vibration and on two and three dimensional analyses of unsteady incompressible viscous flow past oscillating helicopter rotor blades. A summary is presented of the two international research collaborations which resulted from the NASA project: the collaboration under the auspices of NATO between the University of Wisconsin-Milwaukee, University of Brussels, Belgium and the Aerodynamics Research Establishment in Goettingen, West Germany, and the collaboration under the auspices of the National Science Foundation between UWM and the University of Hamburg and the Ship Research Establishment in Hamburg, West Germany. A summary is given of the benefits from the NASA project to UWM, the College of Engineering and Applied Science, and the participants on the project.

  11. Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2002-01-01

    Thick rubber components are employed by the Army to carry large loads. In tanks, rubber covers road wheels and track systems to protect roadways. It is difficult for design engineers to simulate the details of the hysteretic heating for large strain viscoelastic deformations. In this study, an approximation to the viscoelastic energy dissipated per unit time is investigated for use in estimating mechanically induced viscoelastic heating. Coupled thermo-mechanical simulations of large cyclic deformations of rubber cylinders are presented. The cylinders are first compressed axially and then cyclically loaded about the compressed state. Details of the algorithm and some computational issues are discussed. The coupled analyses are conducted for tall and short rubber cylinders both with and without imbedded metal disks.

  12. PSExplorer: whole parameter space exploration for molecular signaling pathway dynamics

    PubMed Central

    Tung, Thai Quang; Lee, Doheon

    2010-01-01

    Motivation: Mathematical models of biological systems often have a large number of parameters whose combinational variations can yield distinct qualitative behaviors. Since it is intractable to examine all possible combinations of parameters for non-trivial biological pathways, it is required to have a systematic strategy to explore the parameter space in a computational way so that dynamic behaviors of a given pathway are estimated. Results: We present PSExplorer, a computational tool for exploring qualitative behaviors and key parameters of molecular signaling pathways. Utilizing the Latin hypercube sampling and a clustering technique in a recursive paradigm, the software enables users to explore the whole parameter space of the models to search for robust qualitative behaviors. The parameter space is partitioned into sub-regions according to behavioral differences. Sub-regions showing robust behaviors can be identified for further analyses. The partitioning result presents a tree structure from which individual and combinational effects of parameters on model behaviors can be assessed and key factors of the models are readily identified. Availability: The software, tutorial manual and test models are available for download at the following address: http://gto.kaist.ac.kr/∼psexplorer Contact: tqtung@kaist.ac.kr; tqtung@gmail.com PMID:20679335

  13. PSExplorer: whole parameter space exploration for molecular signaling pathway dynamics.

    PubMed

    Tung, Thai Quang; Lee, Doheon

    2010-10-01

    Mathematical models of biological systems often have a large number of parameters whose combinational variations can yield distinct qualitative behaviors. Since it is intractable to examine all possible combinations of parameters for non-trivial biological pathways, it is required to have a systematic strategy to explore the parameter space in a computational way so that dynamic behaviors of a given pathway are estimated. We present PSExplorer, a computational tool for exploring qualitative behaviors and key parameters of molecular signaling pathways. Utilizing the Latin hypercube sampling and a clustering technique in a recursive paradigm, the software enables users to explore the whole parameter space of the models to search for robust qualitative behaviors. The parameter space is partitioned into sub-regions according to behavioral differences. Sub-regions showing robust behaviors can be identified for further analyses. The partitioning result presents a tree structure from which individual and combinational effects of parameters on model behaviors can be assessed and key factors of the models are readily identified. The software, tutorial manual and test models are available for download at the following address: http://gto.kaist.ac.kr/∼psexplorer.

  14. Tuning positive feedback for signal detection in noisy dynamic environments.

    PubMed

    Johansson, Anders; Ramsch, Kai; Middendorf, Martin; Sumpter, David J T

    2012-09-21

    Learning from previous actions is a key feature of decision-making. Diverse biological systems, from neuronal assemblies to insect societies, use a combination of positive feedback and forgetting of stored memories to process and respond to input signals. Here we look how these systems deal with a dynamic two-armed bandit problem of detecting a very weak signal in the presence of a high degree of noise. We show that by tuning the form of positive feedback and the decay rate to appropriate values, a single tracking variable can effectively detect dynamic inputs even in the presence of a large degree of noise. In particular, we show that when tuned appropriately a simple positive feedback algorithm is Fisher efficient, in that it can track changes in a signal on a time of order L(h)=(|h|/σ)(-2), where |h| is the magnitude of the signal and σ the magnitude of the noise. Copyright © 2012. Published by Elsevier Ltd.

  15. Analysing the temporal dynamics of model performance for hydrological models

    NASA Astrophysics Data System (ADS)

    Reusser, D. E.; Blume, T.; Schaefli, B.; Zehe, E.

    2009-07-01

    The temporal dynamics of hydrological model performance gives insights into errors that cannot be obtained from global performance measures assigning a single number to the fit of a simulated time series to an observed reference series. These errors can include errors in data, model parameters, or model structure. Dealing with a set of performance measures evaluated at a high temporal resolution implies analyzing and interpreting a high dimensional data set. This paper presents a method for such a hydrological model performance assessment with a high temporal resolution and illustrates its application for two very different rainfall-runoff modeling case studies. The first is the Wilde Weisseritz case study, a headwater catchment in the eastern Ore Mountains, simulated with the conceptual model WaSiM-ETH. The second is the Malalcahuello case study, a headwater catchment in the Chilean Andes, simulated with the physics-based model Catflow. The proposed time-resolved performance assessment starts with the computation of a large set of classically used performance measures for a moving window. The key of the developed approach is a data-reduction method based on self-organizing maps (SOMs) and cluster analysis to classify the high-dimensional performance matrix. Synthetic peak errors are used to interpret the resulting error classes. The final outcome of the proposed method is a time series of the occurrence of dominant error types. For the two case studies analyzed here, 6 such error types have been identified. They show clear temporal patterns, which can lead to the identification of model structural errors.

  16. Analysing the temporal dynamics of model performance for hydrological models

    NASA Astrophysics Data System (ADS)

    Reusser, D. E.; Blume, T.; Schaefli, B.; Zehe, E.

    2008-11-01

    The temporal dynamics of hydrological model performance gives insights into errors that cannot be obtained from global performance measures assigning a single number to the fit of a simulated time series to an observed reference series. These errors can include errors in data, model parameters, or model structure. Dealing with a set of performance measures evaluated at a high temporal resolution implies analyzing and interpreting a high dimensional data set. This paper presents a method for such a hydrological model performance assessment with a high temporal resolution and illustrates its application for two very different rainfall-runoff modeling case studies. The first is the Wilde Weisseritz case study, a headwater catchment in the eastern Ore Mountains, simulated with the conceptual model WaSiM-ETH. The second is the Malalcahuello case study, a headwater catchment in the Chilean Andes, simulated with the physics-based model Catflow. The proposed time-resolved performance assessment starts with the computation of a large set of classically used performance measures for a moving window. The key of the developed approach is a data-reduction method based on self-organizing maps (SOMs) and cluster analysis to classify the high-dimensional performance matrix. Synthetic peak errors are used to interpret the resulting error classes. The final outcome of the proposed method is a time series of the occurrence of dominant error types. For the two case studies analyzed here, 6 such error types have been identified. They show clear temporal patterns which can lead to the identification of model structural errors.

  17. Regulation of Mitoflash Biogenesis and Signaling by Mitochondrial Dynamics

    PubMed Central

    Li, Wenwen; Sun, Tao; Liu, Beibei; Wu, Di; Qi, Wenfeng; Wang, Xianhua; Ma, Qi; Cheng, Heping

    2016-01-01

    Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation. In Drp1- or Mff-deficient cells whose mitochondria hyperfused into a single whole-cell reticulum, the frequency of mitoflashes of regular amplitude and duration was again unaltered, although brief and low-amplitude “miniflashes” emerged because of improved detection ability. As the network reorganized, however, the signal mass of mitoflash signaling was dynamically regulated in accordance with the degree of network connectivity. These findings demonstrate a novel functional role of mitochondrial network dynamics and uncover a magnitude- rather than frequency-modulatory mechanism in the regulation of mitoflash signaling. In addition, our data support a stochastic trigger model for the ignition of mitoflashes. PMID:27623243

  18. Multipoint laser Doppler vibrometry with single detector: principles, implementations, and signal analyses.

    PubMed

    Fu, Y; Guo, M; Phua, P B

    2011-04-01

    A 20-point laser Doppler vibrometer with single photodetector is presented for noncontact dynamic measurement. A 5×4 beam array with various frequency shifts is generated by a 1.55 μm distributed feedback laser and four acousto-optic devices, and illuminating different points on vibrating objects. The reflected beams are coupled into a single-mode fiber by a pigtailed collimator and interfere with a reference beam. The signal output from a high-speed photodetector is amplified and then digitized by a high-speed analog-to-digital converter with a sampling rate of 1 gigasample per second (1 GS/s). Several methods are introduced to avoid the cross talk among different frequencies and extract the vibration information of 20 points from a one-dimensional signal. Two signal processing algorithms based on Fourier transform and windowed Fourier transform are illustrated to extract the vibration signals at different points. The experimental results are compared with that from a commercial single-point laser vibrometer. The results show simultaneous vibration measurement can be realized on multiple points using a single laser source and a single photodetector. © 2011 Optical Society of America

  19. Single-Molecule Protein Conformational Dynamics in Cell Signaling

    SciTech Connect

    Lu, H PETER.

    2004-08-22

    We have demonstrated the application of single-molecule imaging and ultrafast spectroscopy to probe protein conformational dynamics in solution and in lipid bilayers. Dynamic protein-protein interactions involve significant conformational motions that initiate chain reactions leading to specific cellular responses. We have carried out a single molecule study of dynamic protein-protein interactions in a GTPase intracellular signaling protein Cdc42 in complex with a downstream effector protein, WASP. We were able to probe hydrophobic interactions significant to Cdc42/WASP recognition. Single molecule fluorescence intensity and polarization measurements have revealed the dynamic and inhomogeneous nature of protein-protein interactions within the Cdc42/WASP complex that is characterized by structured distributions of conformational fluctuation rates. Conducting a single-molecule fluorescence anisotropy study of calmodulin (CaM), a regulatory protein for calcium-dependent cell signaling, we were able to probe CaM conformational dynamics at a wide time scale. In this study, CaM contains a site-specifically inserted tetra-cysteine motif that reacted with FlAsH, a biarsenic fluorescein derivative that can be rotationally locked to the host protein. The study provided direct characterization of the nanosecond motions of CaM tethered to a biologically compatible surface under physiological buffer solution. The unique technical approaches are applicable of studying single-molecule dynamics of protein conformational motions and protein-protein interactions at a wide time range without the signal convolution of probe-dye molecule motions

  20. Dynamic Ca2+ signal modalities in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael; Qian, Xun; Solodushko, Viktoriya

    2012-01-01

    The endothelium is vital to normal vasoregulation. Although acute vasodilation associated with broad endothelial Ca2+ elevation is well-known, the control and targeting of Ca2+ dependent signals in the endothelium is poorly understood. Recent studies have revealed localized IP3-motivated Ca2+ events occurring basally along the intima that may provide the fundamental basis for various endothelial influences. Here, we provide an overview of dynamic endothelial Ca2+ signals and discuss the potential role of these signals in constant endothelial control of arterial tone and the titration of functional responses in vivo. In particular, we focus on the functional architecture contributing to the properties and ultimate impact of these signals and explore new avenues in evaluating their prevalence and specific modalities in intact tissue. Finally, we discuss spatial and temporal effector recruitment through modification of these inherent signals. It is suggested that endothelial Ca2+ signaling is a continuum in which the specific framework of store-release components and cellular targets along the endothelium allows for differential modes of Ca2+ signal expansion and distinctive profiles of effector recruitment. The precise composition and distribution of these inherent components may underlie dynamic endothelial control and specialized functions of different vascular beds. PMID:22443172

  1. Imaging of dynamic ion signaling during root gravitropism.

    PubMed

    Monshausen, Gabriele B

    2015-01-01

    Gravitropic signaling is a complex process that requires the coordinated action of multiple cell types and tissues. Ca(2+) and pH signaling are key components of gravitropic signaling cascades and can serve as useful markers to dissect the molecular machinery mediating plant gravitropism. To monitor dynamic ion signaling, imaging approaches combining fluorescent ion sensors and confocal fluorescence microscopy are employed, which allow the visualization of pH and Ca(2+) changes at the level of entire tissues, while also providing high spatiotemporal resolution. Here, I describe procedures to prepare Arabidopsis seedlings for live cell imaging and to convert a microscope for vertical stage fluorescence microscopy. With this imaging system, ion signaling can be monitored during all phases of the root gravitropic response.

  2. Dynamic analysis of heartbeat rate signals of epileptics using multidimensional phase space reconstruction approach

    NASA Astrophysics Data System (ADS)

    Su, Zhi-Yuan; Wu, Tzuyin; Yang, Po-Hua; Wang, Yeng-Tseng

    2008-04-01

    The heartbeat rate signal provides an invaluable means of assessing the sympathetic-parasympathetic balance of the human autonomic nervous system and thus represents an ideal diagnostic mechanism for detecting a variety of disorders such as epilepsy, cardiac disease and so forth. The current study analyses the dynamics of the heartbeat rate signal of known epilepsy sufferers in order to obtain a detailed understanding of the heart rate pattern during a seizure event. In the proposed approach, the ECG signals are converted into heartbeat rate signals and the embedology theorem is then used to construct the corresponding multidimensional phase space. The dynamics of the heartbeat rate signal are then analyzed before, during and after an epileptic seizure by examining the maximum Lyapunov exponent and the correlation dimension of the attractors in the reconstructed phase space. In general, the results reveal that the heartbeat rate signal transits from an aperiodic, highly-complex behaviour before an epileptic seizure to a low dimensional chaotic motion during the seizure event. Following the seizure, the signal trajectories return to a highly-complex state, and the complex signal patterns associated with normal physiological conditions reappear.

  3. Towards blueprints for network architecture, biophysical dynamics and signal transduction.

    PubMed

    Coombes, Stephen; Doiron, Brent; Josić, Kresimir; Shea-Brown, Eric

    2006-12-15

    We review mathematical aspects of biophysical dynamics, signal transduction and network architecture that have been used to uncover functionally significant relations between the dynamics of single neurons and the networks they compose. We focus on examples that combine insights from these three areas to expand our understanding of systems neuroscience. These range from single neuron coding to models of decision making and electrosensory discrimination by networks and populations and also coincidence detection in pairs of dendrites and dynamics of large networks of excitable dendritic spines. We conclude by describing some of the challenges that lie ahead as the applied mathematics community seeks to provide the tools which will ultimately underpin systems neuroscience.

  4. Quantitative dynamic imaging of immune cell signalling using lentiviral gene transfer.

    PubMed

    Bagnall, J; Boddington, C; Boyd, J; Brignall, R; Rowe, W; Jones, N A; Schmidt, L; Spiller, D G; White, M R H; Paszek, P

    2015-06-01

    Live-cell imaging of fluorescent fusion proteins has transformed our understanding of mammalian cell signalling and function. However, some cellular systems such as immune cells are unsuitable or refractory to many existing transgene delivery methods thus limiting systematic analyses. Here, a flexible lentiviral gene transfer platform for dynamic time-lapse imaging has been developed and validated with single-molecule spectroscopy, mathematical modelling and transcriptomics and used for analysis of a set of inflammation-related signalling networks. Time-lapse imaging of nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STATs) and nuclear factor of activated T-cells (NFAT) in mammalian immune cell lines provided evidence for heterogeneous temporal encoding of inflammatory signals. In particular, the absolute quantification of single-cell responses over time via fluorescent correlation spectroscopy (FCS) showed that NF-κB p65 activation in response to tumour necrosis factor α (TNFα) was differentially encoded in variable amplitude of nuclear translocation between immune and non-immune cells. The absolute number of activated molecules was dictated in part by the cell size, suggesting a morphology-dependent regulatory mechanism. The developed platform will enable further absolute quantitative analyses of the dynamic interactions between signalling networks, in and between individual cells, allowing better integration with mathematical models of signalling networks.

  5. Aggregation Dynamics Using Phase Wave Signals and Branching Patterns

    NASA Astrophysics Data System (ADS)

    Sakaguchi, Hidetsugu; Kusagaki, Takuma

    2016-09-01

    The aggregation dynamics of slime mold is studied using coupled equations of phase ϕ and cell concentration n. Phase waves work as tactic signals for aggregation. Branching structures appear during the aggregation. A stationary branching pattern appears like a river network, if cells are uniformly supplied into the system.

  6. A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants.

    PubMed

    Larrieu, Antoine; Champion, Antony; Legrand, Jonathan; Lavenus, Julien; Mast, David; Brunoud, Géraldine; Oh, Jaesung; Guyomarc'h, Soazig; Pizot, Maxime; Farmer, Edward E; Turnbull, Colin; Vernoux, Teva; Bennett, Malcolm J; Laplaze, Laurent

    2015-01-16

    Activated forms of jasmonic acid (JA) are central signals coordinating plant responses to stresses, yet tools to analyse their spatial and temporal distribution are lacking. Here we describe a JA perception biosensor termed Jas9-VENUS that allows the quantification of dynamic changes in JA distribution in response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a functional Jas motif and proteasome activity. We demonstrate the utility of Jas9-VENUS to analyse responses to JA in planta at a cellular scale, both quantitatively and dynamically. This included using Jas9-VENUS to determine the cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases of JA activity in the root. Our results demonstrate the value of developing quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal data about hormone distribution in response to plant abiotic and biotic stresses.

  7. Dynamic multiprotein assemblies shape the spatial structure of cell signaling.

    PubMed

    Nussinov, Ruth; Jang, Hyunbum

    2014-01-01

    Cell signaling underlies critical cellular decisions. Coordination, efficiency as well as fail-safe mechanisms are key elements. How the cell ensures that these hallmarks are at play are important questions. Cell signaling is often viewed as taking place through discrete and cross-talking pathways; oftentimes these are modularized to emphasize distinct functions. While simple, convenient and clear, such models largely neglect the spatial structure of cell signaling; they also convey inter-modular (or inter-protein) spatial separation that may not exist. Here our thesis is that cell signaling is shaped by a network of multiprotein assemblies. While pre-organized, the assemblies and network are loose and dynamic. They contain transiently-associated multiprotein complexes which are often mediated by scaffolding proteins. They are also typically anchored in the membrane, and their continuum may span the cell. IQGAP1 scaffolding protein which binds proteins including Raf, calmodulin, Mek, Erk, actin, and tens more, with actin shaping B-cell (and likely other) membrane-anchored nanoclusters and allosterically polymerizing in dynamic cytoskeleton formation, and Raf anchoring in the membrane along with Ras, provides a striking example. The multivalent network of dynamic proteins and lipids, with specific interactions forming and breaking, can be viewed as endowing gel-like properties. Collectively, this reasons that efficient, productive and reliable cell signaling takes place primarily through transient, preorganized and cooperative protein-protein interactions spanning the cell rather than stochastic, diffusion-controlled processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Nonlinear Dynamic Analysis of Scalp EEG Epileptic Signals

    NASA Astrophysics Data System (ADS)

    Blanco, Susana A.; Creso, Judith; Figliola, Alejandra; Quiroga, Rodrigo Quian; Rosso, Osvaldo A.

    Noisy signals obtained during a tonic-clonic epileptic seizure, are usually neglected for visual inspection by the physicians due to the presence of muscle artifacts. Although noise obscures completely the recording, information about the underlying brain activity can be obtained by filtering, through the Orthogonal Wavelet Transforms, those frequencies bands associated with muscle activity. After generating a "noise free" signal by removing the muscle artifacts with wavelets, a dynamical analysis of the brain behavior will be performed by using nonlinear dynamics methods. The values for nonlinear metric invariants, like the correlation dimension and the maximum Lyapunov exponent, confirm that the brain dynamical behavior is more ordered during the epileptic seizure than pre-seizure stage.

  9. MRI dynamic range and its compatibility with signal transmission media

    PubMed Central

    Gabr, Refaat E.; Schär, Michael; Edelstein, Arthur D.; Kraitchman, Dara L.; Bottomley, Paul A.; Edelstein, William A.

    2010-01-01

    As the number of MRI phased array coil elements grows, interactions among cables connecting them to the system receiver become increasingly problematic. Fiber optic or wireless links would reduce electromagnetic interference, but their dynamic range (DR) is generally less than that of coaxial cables. Raw MRI signals, however, have a large DR because of the high signal amplitude near the center of k-space. Here, we study DR in MRI in order to determine the compatibility of MRI multicoil imaging with non-coaxial cable signal transmission. Since raw signal data are routinely discarded, we have developed an improved method for estimating the DR of MRI signals from conventional magnitude images. Our results indicate that the DR of typical surface coil signals at 3 T for human subjects is less than 88 dB, even for three-dimensional acquisition protocols. Cardiac and spine coil arrays had a maximum DR of less than 75 dB and head coil arrays less than 88 dB. The DR derived from magnitude images is in good agreement with that measured from raw data. The results suggest that current analog fiber optic links, with a spurious-free DR of 60–70 dB at 500 kHz bandwidth, are not by themselves adequate for transmitting MRI data from volume or array coils with DR ~90 dB. However, combining analog links with signal compression might make non-coaxial cable signal transmission viable. PMID:19251444

  10. An Integrated Signaling-Encryption Mechanism to Reduce Error Propagation in Wireless Communications: Performance Analyses

    SciTech Connect

    Olama, Mohammed M; Matalgah, Mustafa M; Bobrek, Miljko

    2015-01-01

    Traditional encryption techniques require packet overhead, produce processing time delay, and suffer from severe quality of service deterioration due to fades and interference in wireless channels. These issues reduce the effective transmission data rate (throughput) considerably in wireless communications, where data rate with limited bandwidth is the main constraint. In this paper, performance evaluation analyses are conducted for an integrated signaling-encryption mechanism that is secure and enables improved throughput and probability of bit-error in wireless channels. This mechanism eliminates the drawbacks stated herein by encrypting only a small portion of an entire transmitted frame, while the rest is not subject to traditional encryption but goes through a signaling process (designed transformation) with the plaintext of the portion selected for encryption. We also propose to incorporate error correction coding solely on the small encrypted portion of the data to drastically improve the overall bit-error rate performance while not noticeably increasing the required bit-rate. We focus on validating the signaling-encryption mechanism utilizing Hamming and convolutional error correction coding by conducting an end-to-end system-level simulation-based study. The average probability of bit-error and throughput of the encryption mechanism are evaluated over standard Gaussian and Rayleigh fading-type channels and compared to the ones of the conventional advanced encryption standard (AES).

  11. Translatome analyses capture of opposing tissue-specific brassinosteroid signals orchestrating root meristem differentiation.

    PubMed

    Vragović, Kristina; Sela, Ayala; Friedlander-Shani, Lilach; Fridman, Yulia; Hacham, Yael; Holland, Neta; Bartom, Elizabeth; Mockler, Todd C; Savaldi-Goldstein, Sigal

    2015-01-20

    The mechanisms ensuring balanced growth remain a critical question in developmental biology. In plants, this balance relies on spatiotemporal integration of hormonal signaling pathways, but the understanding of the precise contribution of each hormone is just beginning to take form. Brassinosteroid (BR) hormone is shown here to have opposing effects on root meristem size, depending on its site of action. BR is demonstrated to both delay and promote onset of stem cell daughter differentiation, when acting in the outer tissue of the root meristem, the epidermis, and the innermost tissue, the stele, respectively. To understand the molecular basis of this phenomenon, a comprehensive spatiotemporal translatome mapping of Arabidopsis roots was performed. Analyses of wild type and mutants featuring different distributions of BR revealed autonomous, tissue-specific gene responses to BR, implying its contrasting tissue-dependent impact on growth. BR-induced genes were primarily detected in epidermal cells of the basal meristem zone and were enriched by auxin-related genes. In contrast, repressed BR genes prevailed in the stele of the apical meristem zone. Furthermore, auxin was found to mediate the growth-promoting impact of BR signaling originating in the epidermis, whereas BR signaling in the stele buffered this effect. We propose that context-specific BR activity and responses are oppositely interpreted at the organ level, ensuring coherent growth.

  12. Discrete dynamic modeling of T cell survival signaling networks

    NASA Astrophysics Data System (ADS)

    Zhang, Ranran

    2009-03-01

    Biochemistry-based frameworks are often not applicable for the modeling of heterogeneous regulatory systems that are sparsely documented in terms of quantitative information. As an alternative, qualitative models assuming a small set of discrete states are gaining acceptance. This talk will present a discrete dynamic model of the signaling network responsible for the survival and long-term competence of cytotoxic T cells in the blood cancer T-LGL leukemia. We integrated the signaling pathways involved in normal T cell activation and the known deregulations of survival signaling in leukemic T-LGL, and formulated the regulation of each network element as a Boolean (logic) rule. Our model suggests that the persistence of two signals is sufficient to reproduce all known deregulations in leukemic T-LGL. It also indicates the nodes whose inactivity is necessary and sufficient for the reversal of the T-LGL state. We have experimentally validated several model predictions, including: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of T cells in T-LGL leukemia. (iii) T box expressed in T cells (T-bet) is constitutively activated in the T-LGL state. The model has identified potential therapeutic targets for T-LGL leukemia and can be used for generating long-term competent CTL necessary for tumor and cancer vaccine development. The success of this model, and of other discrete dynamic models, suggests that the organization of signaling networks has an determining role in their dynamics. Reference: R. Zhang, M. V. Shah, J. Yang, S. B. Nyland, X. Liu, J. K. Yun, R. Albert, T. P. Loughran, Jr., Network Model of Survival Signaling in LGL Leukemia, PNAS 105, 16308-16313 (2008).

  13. Probing the dynamic nature of signalling pathways by IMAC and SELDI-tof MS.

    PubMed

    Foucher, Aude L; Späth, Gerald F; Pemberton, Iain K

    2010-01-01

    One major obstacle to the analysis of signalling pathways is the dynamic nature of signalling response to environmental stimuli. To overcome this limitation we applied immobilized metal affinity chromatography (IMAC) in combination with SELDI-tof MS to investigate the temporal variation of protein phosphorylation. We analysed the phospho-proteome variations in our model organism, Leishmania donovani, in response to changes in pH and temperature, which induce differentiation from promastigotes to amastigotes. Investigation of total cell extracts did not allow promastigote and amastigote life cycle stages to be distinguished. However, using IMAC enriched samples, the pattern and intensity of phospho-proteins analysed distinguished both stages reproducibly. Approximately 61% of the phospho-proteins analysed were significantly different in abundance (p<0.02). Of these 61%, 73% showed an increased phosphorylation in promastigotes while 27% showed an increase phosphorylation in amastigotes. The workflow developed is currently being applied to the temporal analysis of environmental stimuli.

  14. Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics.

    PubMed

    Pizzo, Paola; Pozzan, Tullio

    2007-10-01

    Mitochondria and endoplasmic reticulum (ER) have different roles in living cells but they interact both physically and functionally. A key aspect of the mitochondria-ER relationship is the modulation of Ca(2+) signaling during cell activation, which thus affects a variety of physiological processes. We focus here on the molecular aspects that control the dynamics of the organelle-organelle interaction and their relationship with Ca(2+) signals, also discussing the consequences that these phenomena have, not only for cell physiology but also in the control of cell death.

  15. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator.

    PubMed

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-08-31

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver's reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σ(FLL)). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σ(FLL)). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers.

  16. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator

    PubMed Central

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-01-01

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver’s reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σFLL). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σFLL). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers. PMID:26404286

  17. Systematic Characterization of Dynamic Parameters of Intracellular Calcium Signals

    PubMed Central

    Mackay, Laurent; Mikolajewicz, Nicholas; Komarova, Svetlana V.; Khadra, Anmar

    2016-01-01

    Dynamic processes, such as intracellular calcium signaling, are hallmark of cellular biology. As real-time imaging modalities become widespread, a need for analytical tools to reliably characterize time-series data without prior knowledge of the nature of the recordings becomes more pressing. The goal of this study is to develop a signal-processing algorithm for MATLAB that autonomously computes the parameters characterizing prominent single transient responses (TR) and/or multi-peaks responses (MPR). The algorithm corrects for signal contamination and decomposes experimental recordings into contributions from drift, TRs, and MPRs. It subsequently provides numerical estimates for the following parameters: time of onset after stimulus application, activation time (time for signal to increase from 10 to 90% of peak), and amplitude of response. It also provides characterization of the (i) TRs by quantifying their area under the curve (AUC), response duration (time between 1/2 amplitude on ascent and descent of the transient), and decay constant of the exponential decay region of the deactivation phase of the response, and (ii) MPRs by quantifying the number of peaks, mean peak magnitude, mean periodicity, standard deviation of periodicity, oscillatory persistence (time between first and last discernable peak), and duty cycle (fraction of period during which system is active) for all the peaks in the signal, as well as coherent oscillations (i.e., deterministic spikes). We demonstrate that the signal detection performance of this algorithm is in agreement with user-mediated detection and that parameter estimates obtained manually and algorithmically are correlated. We then apply this algorithm to study how metabolic acidosis affects purinergic (P2) receptor-mediated calcium signaling in osteoclast precursor cells. Our results reveal that acidosis significantly attenuates the amplitude and AUC calcium responses at high ATP concentrations. Collectively, our data

  18. SIGNAL TRANSDUCTION. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling.

    PubMed

    Zhou, Yong; Wong, Ching-On; Cho, Kwang-jin; van der Hoeven, Dharini; Liang, Hong; Thakur, Dhananiay P; Luo, Jialie; Babic, Milos; Zinsmaier, Konrad E; Zhu, Michael X; Hu, Hongzhen; Venkatachalam, Kartik; Hancock, John F

    2015-08-21

    Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.

  19. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    DTIC Science & Technology

    2012-07-01

    VL. Protein Microarray Analysis of Mammary Epithelial Cells from Obese and Non- Obese Women at High-Risk for Breast Cancer . Cancer Epidemiol...from Obese and Non- Obese Women at High-Risk for Breast Cancer . Cancer Epidemiol Biomarkers Prevention. 20:476-482, 2011 (cover article). PMID...Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham

  20. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis

    PubMed Central

    Shin, Sung-Young; Nguyen, Lan K.

    2016-01-01

    The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies. PMID:27527217

  1. The analyses of dynamic response and reliability of fuzzy-random truss under stationary stochastic excitation

    NASA Astrophysics Data System (ADS)

    Ma, Juan; Gao, Wei; Wriggers, Peter; Wu, Tao; Sahraee, Shahab

    2010-04-01

    A new two-factor method based on the probability and the fuzzy sets theory is used for the analyses of the dynamic response and reliability of fuzzy-random truss systems under the stationary stochastic excitation. Considering the fuzzy-randomness of the structural physical parameters and geometric dimensions simultaneously, the fuzzy-random correlation function matrix of structural displacement response in time domain and the fuzzy-random mean square values of structural dynamic response in frequency domain are developed by using the two-factor method, and the fuzzy numerical characteristics of dynamic responses are then derived. Based on numerical characteristics of structural fuzzy-random dynamic responses, the structural fuzzy-random dynamic reliability and its fuzzy numerical characteristic are obtained from the Poisson equation. The effects of the uncertainty of the structural parameters on structural dynamic response and reliability are illustrated via two engineering examples and some important conclusions are obtained.

  2. Environmental odours assessment from waste treatment plants: dynamic olfactometry in combination with sensorial analysers "electronic noses".

    PubMed

    Littarru, Paolo

    2007-01-01

    After an overview about the criteria of odour nuisance in different technical laws, about electronic noses analysers and about dynamic olfactometry, in the present paper the authors describe an application of dynamic olfactometry in combination with the determinations of electronic noses. The coordination of the two approaches permits optimisation of the advantages offered by both methods to the measurable and objective evaluation of the odour nuisance from waste treatment plants and chemical plants.

  3. Signal Transduction at the Single-Cell Level: Approaches to Study the Dynamic Nature of Signaling Networks.

    PubMed

    Handly, L Naomi; Yao, Jason; Wollman, Roy

    2016-09-25

    Signal transduction, or how cells interpret and react to external events, is a fundamental aspect of cellular function. Traditional study of signal transduction pathways involves mapping cellular signaling pathways at the population level. However, population-averaged readouts do not adequately illuminate the complex dynamics and heterogeneous responses found at the single-cell level. Recent technological advances that observe cellular response, computationally model signaling pathways, and experimentally manipulate cells now enable studying signal transduction at the single-cell level. These studies will enable deeper insights into the dynamic nature of signaling networks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Fault diagnosis of motor drives using stator current signal analysis based on dynamic time warping

    NASA Astrophysics Data System (ADS)

    Zhen, D.; Wang, T.; Gu, F.; Ball, A. D.

    2013-01-01

    Electrical motor stator current signals have been widely used to monitor the condition of induction machines and their downstream mechanical equipment. The key technique used for current signal analysis is based on Fourier transform (FT) to extract weak fault sideband components from signals predominated with supply frequency component and its higher order harmonics. However, the FT based method has limitations such as spectral leakage and aliasing, leading to significant errors in estimating the sideband components. Therefore, this paper presents the use of dynamic time warping (DTW) to process the motor current signals for detecting and quantifying common faults in a downstream two-stage reciprocating compressor. DTW is a time domain based method and its algorithm is simple and easy to be embedded into real-time devices. In this study DTW is used to suppress the supply frequency component and highlight the sideband components based on the introduction of a reference signal which has the same frequency component as that of the supply power. Moreover, a sliding window is designed to process the raw signal using DTW frame by frame for effective calculation. Based on the proposed method, the stator current signals measured from the compressor induced with different common faults and under different loads are analysed for fault diagnosis. Results show that DTW based on residual signal analysis through the introduction of a reference signal allows the supply components to be suppressed well so that the fault related sideband components are highlighted for obtaining accurate fault detection and diagnosis results. In particular, the root mean square (RMS) values of the residual signal can indicate the differences between the healthy case and different faults under varying discharge pressures. It provides an effective and easy approach to the analysis of motor current signals for better fault diagnosis of the downstream mechanical equipment of motor drives in the time

  5. Interrogating the signaling dynamics of T cell activation with quantum dots

    NASA Astrophysics Data System (ADS)

    Warnement, Michael R.; Faley, Shannon L.; Wikswo, John P.; Rosenthal, Sandra J.

    2006-02-01

    We report the use of antibody-conjugated quantum dots (QDs) to monitor the expression dynamics of the membrane bound cytokine receptor interleukin-2 receptor-α (IL-2Rα) throughout the course of Jurkat T cell activation. Maximal receptor expression is observed 32-48 hours after activation, followed by a sharp decrease subsequent to 48 hours consistent with IL-2R internalization. Fluorescence microscopy, ELISA, and FACS analyses were used to verify controlled activation and specificity of QD labeling. Additionally, confocal microscopy demonstrated receptor internalization subsequent to expression and QD labeling. Antibody-conjugated QDs provide a convenient means to rapidly determine cell state and interrogate end products of cell signaling pathways. Interrogation of other signaling pathways can eventually be carried out in a similar manner upon identification of relevant membrane associated receptors. Ultimately, the multiplexing capabilities of QDs will allow the examination of several signaling pathways simultaneously and aid in toxin detection and discrimination.

  6. Luminal Ca2+ dynamics during IP3R mediated signals

    NASA Astrophysics Data System (ADS)

    Lopez, Lucia F.; Ponce Dawson, Silvina

    2016-06-01

    The role of cytosolic Ca2+ on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca2+ signals has been studied at large both experimentally and by modeling. The role of luminal Ca2+ has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca2+ release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca2+ simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca2+ in the lumen even when a relatively large Ca2+ release is evoked. Comparing the dynamics of cytosolic and luminal Ca2+ during a release, we estimate that they are consistent with a 80% of luminal Ca2+ being buffered. The rapid availability of free luminal Ca2+ correlates with the observation that the lumen occupies a considerable volume in several regions across the images.

  7. Single-block rockfall dynamics inferred from seismic signal analysis

    NASA Astrophysics Data System (ADS)

    Hibert, Clément; Malet, Jean-Philippe; Bourrier, Franck; Provost, Floriane; Berger, Frédéric; Bornemann, Pierrick; Tardif, Pascal; Mermin, Eric

    2017-05-01

    Seismic monitoring of mass movements can significantly help to mitigate the associated hazards; however, the link between event dynamics and the seismic signals generated is not completely understood. To better understand these relationships, we conducted controlled releases of single blocks within a soft-rock (black marls) gully of the Rioux-Bourdoux torrent (French Alps). A total of 28 blocks, with masses ranging from 76 to 472 kg, were used for the experiment. An instrumentation combining video cameras and seismometers was deployed along the travelled path. The video cameras allow reconstructing the trajectories of the blocks and estimating their velocities at the time of the different impacts with the slope. These data are compared to the recorded seismic signals. As the distance between the falling block and the seismic sensors at the time of each impact is known, we were able to determine the associated seismic signal amplitude corrected for propagation and attenuation effects. We compared the velocity, the potential energy lost, the kinetic energy and the momentum of the block at each impact to the true amplitude and the radiated seismic energy. Our results suggest that the amplitude of the seismic signal is correlated to the momentum of the block at the impact. We also found relationships between the potential energy lost, the kinetic energy and the seismic energy radiated by the impacts. Thanks to these relationships, we were able to retrieve the mass and the velocity before impact of each block directly from the seismic signal. Despite high uncertainties, the values found are close to the true values of the masses and the velocities of the blocks. These relationships allow for gaining a better understanding of the physical processes that control the source of high-frequency seismic signals generated by rockfalls.

  8. Lipid signalling dynamics at the β-cell plasma membrane.

    PubMed

    Wuttke, Anne

    2015-04-01

    Pancreatic β-cells are clustered in islets of Langerhans and secrete insulin in response to increased concentrations of circulating glucose. Insulin in turn acts on liver, muscle and fat tissue to store energy and normalize the blood glucose level. Inappropriate insulin release may lead to impaired glucose tolerance and diabetes. In addition to glucose, other nutrients, neural stimuli and hormonal stimuli control insulin secretion. Many of these signals are perceived at the plasma membrane, which is also the site where insulin granules undergo exocytosis. Therefore, it is not surprising that membrane lipids play an important role in the regulation of insulin secretion. β-cells release insulin in a pulsatile fashion. Signalling lipids integrate the nutrient and neurohormonal inputs to fine-tune, shape and co-ordinate the pulsatility. An important group of signalling lipids are phosphoinositides and their downstream messengers. This MiniReview will discuss new insights into lipid signalling dynamics in β-cells obtained from live-cell imaging experiments with fluorescent translocation biosensors. The plasma membrane concentration of several phosphoinositides and of their downstream messengers changes rapidly upon nutrient or neurohormonal stimulation. Glucose induces the most complex spatio-temporal patterns, typically involving oscillations of messenger concentrations, which sometimes are locally restricted. The tightly controlled levels of lipid messengers can mediate specific binding of downstream effectors to the plasma membrane, contributing to the appropriate regulation of insulin secretion. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  9. Dynamic functions of GABA signaling during granule cell maturation

    PubMed Central

    Dieni, Cristina V.; Chancey, Jessica H.; Overstreet-Wadiche, Linda S.

    2013-01-01

    The dentate gyrus is one of the few areas of the brain where new neurons are generated throughout life. Neural activity influences multiple stages of neurogenesis, thereby allowing experience to regulate the production of new neurons. It is now well established that GABAA receptor-mediated signaling plays a pivotal role in mediating activity-dependent regulation of adult neurogenesis. GABA first acts as a trophic signal that depolarizes progenitors and early post mitotic granule cells, enabling network activity to control molecular cascades essential for proliferation, survival and growth. Following the development of glutamatergic synaptic inputs, GABA signaling switches from excitatory to inhibitory. Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region. Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages. We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability. PMID:23316139

  10. Structural Dynamics of Insulin Receptor and Transmembrane Signaling.

    PubMed

    Tatulian, Suren A

    2015-09-15

    The insulin receptor (IR) is a (αβ)2-type transmembrane tyrosine kinase that plays a central role in cell metabolism. Each αβ heterodimer consists of an extracellular ligand-binding α-subunit and a membrane-spanning β-subunit that comprises the cytoplasmic tyrosine kinase (TK) domain and the phosphorylation sites. The α- and β-subunits are linked via a single disulfide bridge, and the (αβ)2 tetramer is formed by disulfide bonds between the α-chains. Insulin binding induces conformational changes in IR that reach the intracellular β-subunit followed by a protein phosphorylation and activation cascade. Defects in this signaling process, including IR dysfunction caused by mutations, result in type 2 diabetes. Rational drug design aimed at treatment of diabetes relies on knowledge of the detailed structure of IR and the dynamic structural transformations during transmembrane signaling. Recent X-ray crystallographic studies have provided important clues about the mode of binding of insulin to IR, the resulting structural changes and their transmission to the TK domain, but a complete understanding of the structural basis underlying insulin signaling has not been achieved. This review presents a critical analysis of the current status of the structure-function relationship of IR, with a comparative assessment of the other IR family receptors, and discusses potential advancements that may provide insight into the molecular mechanism of insulin signaling.

  11. Evolving from static to dynamic signals: evolutionary compensation between two communicative signals

    PubMed Central

    Martins, Emília P.; Ossip-Klein, Alison G.; Zúñiga-Vega, J. Jaime; García, Cuauhcihuatl Vital; Campos, Stephanie M.; Hews, Diana K.

    2015-01-01

    Signals that convey related information may impose selection on each other, creating evolutionary links between different components of the communicative repertoire. Here, we ask about the consequences of the evolutionary loss of one signal (a colour patch) on another (a motion display) in Sceloporus lizards. We present data on male lizards of four species: two pairs of sister taxa representing two independent evolutionary losses of the static colour patch (Sceloporus cozumelae and Sceloporus parvus; Sceloporus siniferus and Sceloporus merriami). Males of the two species that have undergone an evolutionary loss of blue-belly patches (S. cozumelae, S. siniferus) were less active than their blue-bellied sister taxa (S. parvus, S. merriami), consistent with the suggestion that the belly patches were lost to reduce conspicuousness of species with high predation pressure. In contrast, the headbob display appears to have become more, rather than less, conspicuous over evolutionary time. The colour patch is exhibited primarily during aggressive encounters, whereas headbob displays are multifunction signals used in several different contexts, including aggressive encounters. Males of species that have lost the colour patch produced more motion displays, and the structure of those motion displays were more similar to those produced during combat. In both evolutionary episodes, a static colour signal appears to have been replaced by dynamic motion displays that can be turned off in the presence of predators and other unwanted receivers. The predominant pattern is one of evolutionary compensation and interactions between multiple signals that convey related information. PMID:25892737

  12. Evolving from static to dynamic signals: evolutionary compensation between two communicative signals.

    PubMed

    Martins, Emília P; Ossip-Klein, Alison G; Zúñiga-Vega, J Jaime; García, Cuauhcihuatl Vital; Campos, Stephanie M; Hews, Diana K

    2015-04-01

    Signals that convey related information may impose selection on each other, creating evolutionary links between different components of the communicative repertoire. Here, we ask about the consequences of the evolutionary loss of one signal (a colour patch) on another (a motion display) in Sceloporus lizards. We present data on male lizards of four species: two pairs of sister taxa representing two independent evolutionary losses of the static colour patch (Sceloporus cozumelae and Sceloporus parvus; Sceloporus siniferus and Sceloporus merriami). Males of the two species that have undergone an evolutionary loss of blue-belly patches (S. cozumelae, S. siniferus) were less active than their blue-bellied sister taxa (S. parvus, S. merriami), consistent with the suggestion that the belly patches were lost to reduce conspicuousness of species with high predation pressure. In contrast, the headbob display appears to have become more, rather than less, conspicuous over evolutionary time. The colour patch is exhibited primarily during aggressive encounters, whereas headbob displays are multifunction signals used in several different contexts, including aggressive encounters. Males of species that have lost the colour patch produced more motion displays, and the structure of those motion displays were more similar to those produced during combat. In both evolutionary episodes, a static colour signal appears to have been replaced by dynamic motion displays that can be turned off in the presence of predators and other unwanted receivers. The predominant pattern is one of evolutionary compensation and interactions between multiple signals that convey related information.

  13. Comparisons of several aerodynamic methods for application to dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Kroll, R. I.; Miller, R. D.

    1976-01-01

    The results of a study are presented in which the applicability at subsonic speeds of several aerodynamic methods for predicting dynamic gust loads on aircraft, including active control systems, was examined and compared. These aerodynamic methods varied from steady state to an advanced unsteady aerodynamic formulation. Brief descriptions of the structural and aerodynamic representations and of the motion and load equations are presented. Comparisons of numerical results achieved using the various aerodynamic methods are shown in detail. From these results, aerodynamic representations for dynamic gust analyses are identified. It was concluded that several aerodynamic methods are satisfactory for dynamic gust analyses of configurations having either controls fixed or active control systems that primarily affect the low frequency rigid body aircraft response.

  14. Multiparticle collision dynamics for diffusion-influenced signaling pathways

    NASA Astrophysics Data System (ADS)

    Strehl, R.; Rohlf, K.

    2016-08-01

    An efficient yet accurate simulation method for modeling diffusion-influenced reaction networks is presented. The method extends existing reactive multiparticle collision dynamics by incorporating species-dependent diffusion coefficients, and developing theoretical expressions for the reactant-dependent diffusion control. This off-lattice particle-based mesoscopic simulation tool is particularly suited for problems in which detailed descriptions of particle trajectories and local reactions are required. Numerical simulations of an intracellular signaling pathway for bacterial chemotaxis are carried out to validate our approach, and to demonstrate its efficiency.

  15. Pinning down response inhibition in the brain – conjunction analyses of the Stop-signal task

    PubMed Central

    Boehler, CN; Appelbaum, LG; Krebs, RM; Hopf, JM; Woldorff, MG

    2010-01-01

    Successful behavior requires a finely-tuned interplay of initiating and inhibiting motor programs to react effectively to constantly changing environmental demands. One particularly useful paradigm for investigating inhibitory motor control is the Stop-signal task, where already-initiated responses to Go-stimuli are to be inhibited upon the rapid subsequent presentation of a Stop-stimulus (yielding successful and unsuccessful Stop-trials). Despite the extensive use of this paradigm in functional neuroimaging, there is no consensus on which functional comparison to use to characterize response-inhibition-related brain activity. Here, we utilize conjunction analyses of successful and unsuccessful Stop-trials that are each contrasted against a reference condition. This conjunction approach identifies processes common to both Stop-trial types while excluding processes specific to either, thereby capitalizing on the presence of some response-inhibition-related activity in both conditions. Using this approach on fMRI data from human subjects, we identify a network of brain structures that was linked to both types of Stop-trials, including lateral-inferior-frontal and medial-frontal cortical areas and the caudate nucleus. In addition, comparisons with a reference condition matched for visual stimulation identified additional activity in the right inferior parietal cortex that may play a role in enhancing the processing of the Stop-stimuli. Finally, differences in stopping efficacy across subjects were associated with variations in activity in the left anterior insula. However, this region was also associated with general task accuracy (which furthermore correlated directly with stopping efficacy), suggesting that it might actually reflect a more general mechanism of performance control that supports response inhibition in a relatively nonspecific way. PMID:20452445

  16. Characterizing rhodopsin signaling by EPR spectroscopy: from structure to dynamics.

    PubMed

    Van Eps, Ned; Caro, Lydia N; Morizumi, Takefumi; Ernst, Oliver P

    2015-09-26

    Electron paramagnetic resonance (EPR) spectroscopy, together with spin labeling techniques, has played a major role in the characterization of rhodopsin, the photoreceptor protein and G protein-coupled receptor (GPCR) in rod cells. Two decades ago, these biophysical tools were the first to identify transmembrane helical movements in rhodopsin upon photo-activation, a critical step in the study of GPCR signaling. EPR methods were employed to identify functional loop dynamics within rhodopsin, to measure light-induced millisecond timescale changes in rhodopsin conformation, to characterize the effects of partial agonists on the apoprotein opsin, and to study lipid interactions with rhodopsin. With the emergence of advanced pulsed EPR techniques, the stage was set to determine the amplitude of structural changes in rhodopsin and the dynamics in the rhodopsin signaling complexes. Work in this area has yielded invaluable information about mechanistic properties of GPCRs. Using EPR techniques, receptors are studied in native-like membrane environments and the effects of lipids on conformational equilibria can be explored. This perspective addresses the impact of EPR methods on rhodopsin and GPCR structural biology, highlighting historical discoveries made with spin labeling techniques, and outlining exciting new directions in the field.

  17. Promoter nucleosome dynamics regulated by signalling through the CTD code

    PubMed Central

    Materne, Philippe; Anandhakumar, Jayamani; Migeot, Valerie; Soriano, Ignacio; Yague-Sanz, Carlo; Hidalgo, Elena; Mignion, Carole; Quintales, Luis; Antequera, Francisco; Hermand, Damien

    2015-01-01

    The phosphorylation of the RNA polymerase II C-terminal domain (CTD) plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phospho-S2 CTD nearby the promoter impairs the phospho-S5 CTD-dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phospho-S2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signalling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signalling through the CTD code regulates promoter nucleosomes dynamics. DOI: http://dx.doi.org/10.7554/eLife.09008.001 PMID:26098123

  18. Dynamic binding of RBPJ is determined by Notch signaling status

    PubMed Central

    Castel, David; Mourikis, Philippos; Bartels, Stefanie J.J.; Brinkman, Arie B.; Tajbakhsh, Shahragim; Stunnenberg, Hendrik G.

    2013-01-01

    Notch signaling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighboring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and, together with the transcription factor moiety of Notch (NICD), regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole-genome binding profiles were generated for RBPJ; its coactivator, p300; NICD; and the histone H3 modifications H3 Lys 4 trimethylation (H3K4me3), H3 Lys 4 monomethylation (H3K4me1), and histone H3 Lys 27 acetylation (H3K27ac) in myogenic cells under active or inhibitory Notch signaling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300 and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signaling mediate their activities and consequently impact on cell fate decisions. PMID:23651858

  19. Signalling and the evolution of cooperative foraging in dynamic environments.

    PubMed

    Torney, Colin J; Berdahl, Andrew; Couzin, Iain D

    2011-09-01

    Understanding cooperation in animal social groups remains a significant challenge for evolutionary theory. Observed behaviours that benefit others but incur some cost appear incompatible with classical notions of natural selection; however, these behaviours may be explained by concepts such as inclusive fitness, reciprocity, intra-specific mutualism or manipulation. In this work, we examine a seemingly altruistic behaviour, the active recruitment of conspecifics to a food resource through signalling. Here collective, cooperative behaviour may provide highly nonlinear benefits to individuals, since group functionality has the potential to be far greater than the sum of the component parts, for example by enabling the effective tracking of a dynamic resource. We show that due to this effect, signalling to others is an evolutionarily stable strategy under certain environmental conditions, even when there is a cost associated to this behaviour. While exploitation is possible, in the limiting case of a sparse, ephemeral but locally abundant nutrient source, a given environmental profile will support a fixed number of signalling individuals. Through a quantitative analysis, this effective carrying capacity for cooperation is related to the characteristic length and time scales of the resource field.

  20. Dynamic shaping of dopamine signals during probabilistic Pavlovian conditioning.

    PubMed

    Hart, Andrew S; Clark, Jeremy J; Phillips, Paul E M

    2015-01-01

    Cue- and reward-evoked phasic dopamine activity during Pavlovian and operant conditioning paradigms is well correlated with reward-prediction errors from formal reinforcement learning models, which feature teaching signals in the form of discrepancies between actual and expected reward outcomes. Additionally, in learning tasks where conditioned cues probabilistically predict rewards, dopamine neurons show sustained cue-evoked responses that are correlated with the variance of reward and are maximal to cues predicting rewards with a probability of 0.5. Therefore, it has been suggested that sustained dopamine activity after cue presentation encodes the uncertainty of impending reward delivery. In the current study we examined the acquisition and maintenance of these neural correlates using fast-scan cyclic voltammetry in rats implanted with carbon fiber electrodes in the nucleus accumbens core during probabilistic Pavlovian conditioning. The advantage of this technique is that we can sample from the same animal and recording location throughout learning with single trial resolution. We report that dopamine release in the nucleus accumbens core contains correlates of both expected value and variance. A quantitative analysis of these signals throughout learning, and during the ongoing updating process after learning in probabilistic conditions, demonstrates that these correlates are dynamically encoded during these phases. Peak CS-evoked responses are correlated with expected value and predominate during early learning while a variance-correlated sustained CS signal develops during the post-asymptotic updating phase. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Signalling protein complexes isolated from primary human skin-resident T cells can be analysed by Multiplex IP-FCM.

    PubMed

    Smith, Stephen E P; Neier, Steven C; Davis, Tessa R; Pittelkow, Mark R; Gil, Diana; Schrum, Adam G

    2014-04-01

    Studying signal transduction in skin-resident T cells (sr-T cells) can be limited by the small size of clinical biopsies. Here, we isolated sr-T cells from clinical samples and analysed signalling protein complexes by multiplex immunoprecipitation detected by flow cytometry (mIP-FCM). In samples from two independent donors, antigenic stimulation induced signalling proteins to join shared complexes that were observed in seven pairwise combinations among five proteins. This demonstrates that sr-T cells isolated from small clinical samples provide sufficient material for mIP-FCM-based analysis of signalling-induced protein complexes. We propose that this strategy may be useful for gaining improved mechanistic insight of sr-T cell signal transduction associated with dermatological disease.

  2. Dynamic signaling cascades: reversible covalent reaction-coupled molecular switches.

    PubMed

    Ren, Yulong; You, Lei

    2015-11-11

    The research of systems chemistry exploring complex mixtures of interacting synthetic molecules has been burgeoning recently. Herein we demonstrate for the first time the coupling of molecular switches with a dynamic covalent reaction (DCR) and the modulation of created chemical cascades with a variety of inputs, thus closely mimicking a biological signaling system. A novel Michael type DCR of 10-methylacridinium perchlorate and monothiols exhibiting excellent regioselectivity and tunable affinity was discovered. A delicate balance between the unique reactivity of the reactant and the stability of the adduct leads to the generation of a strong acid in a thermodynamically controlled system. The dynamic cascade was next created via coupling of the DCR and a protonation-induced configurational switch (E/Z isomerization) through a proton relay. Detailed examination of the interdependence of the equilibrium enabled us to rationally optimize the cascade and also shed light on the possible intermediate of the switching process. Furthermore, relative independence of the coupled reactions was verified by the identification of stimuli that are able to facilitate one reaction but suppress the other. To further enhance systematic complexity, a second DCR of electrophilic aldehydes and thiols was employed for the reversible inhibition of the binary system, thus achieving the interplay of multiple equilibria. Finally, a fluorescence switch was turned on through coupling with the DCR, showcasing the versatility of our strategy. The results described herein should pave the way for the exploitation of multifunctional dynamic covalent cascades.

  3. Optimal BLS: Optimizing transit-signal detection for Keplerian dynamics

    NASA Astrophysics Data System (ADS)

    Ofir, Aviv

    2015-08-01

    Transit surveys, both ground- and space-based, have already accumulated a large number of light curves that span several years. We optimize the search for transit signals for both detection and computational efficiencies by assuming that the searched systems can be described by Keplerian, and propagating the effects of different system parameters to the detection parameters. Importnantly, we mainly consider the information content of the transit signal and not any specific algorithm - and use BLS (Kovács, Zucker, & Mazeh 2002) just as a specific example.We show that the frequency information content of the light curve is primarily determined by the duty cycle of the transit signal, and thus the optimal frequency sampling is found to be cubic and not linear. Further optimization is achieved by considering duty-cycle dependent binning of the phased light curve. By using the (standard) BLS, one is either fairly insensitive to long-period planets or less sensitive to short-period planets and computationally slower by a significant factor of ~330 (for a 3 yr long dataset). We also show how the physical system parameters, such as the host star's size and mass, directly affect transit detection. This understanding can then be used to optimize the search for every star individually.By considering Keplerian dynamics explicitly rather than implicitly one can optimally search the transit signal parameter space. The presented Optimal BLS enhances the detectability of both very short and very long period planets, while allowing such searches to be done with much reduced resources and time. The Matlab/Octave source code for Optimal BLS is made available.

  4. Assessment of Tools and Data for System-Level Dynamic Analyses

    SciTech Connect

    Steven J. Piet; Nick R. Soelberg

    2011-06-01

    The only fuel cycle for which dynamic analyses and assessments are not needed is the null fuel cycle - no nuclear power. For every other concept, dynamic analyses are needed and can influence relative desirability of options. Dynamic analyses show how a fuel cycle might work during transitions from today's partial fuel cycle to something more complete, impact of technology deployments, location of choke points, the key time lags, when benefits can manifest, and how well parts of fuel cycles work together. This report summarizes the readiness of existing Fuel Cycle Technology (FCT) tools and data for conducting dynamic analyses on the range of options. VISION is the primary dynamic analysis tool. Not only does it model mass flows, as do other dynamic system analysis models, but it allows users to explore various potential constraints. The only fuel cycle for which constraints are not important are those in concept advocates PowerPoint presentations; in contrast, comparative analyses of fuel cycles must address what constraints exist and how they could impact performance. The most immediate tool need is extending VISION to the thorium/U233 fuel cycle. Depending on further clarification of waste management strategies in general and for specific fuel cycle candidates, waste management sub-models in VISION may need enhancement, e.g., more on 'co-flows' of non-fuel materials, constraints in waste streams, or automatic classification of waste streams on the basis of user-specified rules. VISION originally had an economic sub-model. The economic calculations were deemed unnecessary in later versions so it was retired. Eventually, the program will need to restore and improve the economics sub-model of VISION to at least the cash flow stage and possibly to incorporating cost constraints and feedbacks. There are multiple sources of data that dynamic analyses can draw on. In this report, 'data' means experimental data, data from more detailed theoretical or empirical

  5. Comparative survey of dynamic analyses of free-piston stirling engines

    SciTech Connect

    Kankam, M.D.; Rauch, J.S.

    1994-09-01

    This paper compares reported dynamic analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  6. Comparative survey of dynamic analyses of free-piston Stirling engines

    NASA Technical Reports Server (NTRS)

    Kankam, M. David; Rauch, Jeffrey S.

    1991-01-01

    Reported dynamics analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems are compared. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  7. Bewaffnete Konflikte: Geschichte, Dynamik, Simulation und Analyse (Armed Conflict: History, Dynamics, Simulation and Analysis)

    DTIC Science & Technology

    2016-04-01

    AMOS) , ISSN-Print 2199-1928 Angewandte Mathematik und Optimierung Schriftenreihe (AMOS) , ISSN- Internet 2199-1936 REPORT DOCUMENTATION PAGE I Form...Konflikte: Gesch ichte, D ynamik, Simulation und Analyse (Armed Conflict: History , Dynamics, Simulation and Analysis) 6 . AUTHOR(S) Armin Fi.igenschuh...Machine assisted translation. 14. SUBJECT TERMS UN1BW , Gennan, anned conflict, history , simu lation , wargami ng, games 17. S ECURITY CLASS IFI CATION

  8. Comparative survey of dynamic analyses of free-piston Stirling engines

    NASA Technical Reports Server (NTRS)

    Kankam, M. D.; Rauch, J. S.

    1991-01-01

    Reported dynamics analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems are compared. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  9. Dynamic neural activity during stress signals resilient coping

    PubMed Central

    Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

    2016-01-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  10. Dynamic neural activity during stress signals resilient coping.

    PubMed

    Sinha, Rajita; Lacadie, Cheryl M; Constable, R Todd; Seo, Dongju

    2016-08-02

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping.

  11. Characterization of landslides dynamics using the generated seismic signal

    NASA Astrophysics Data System (ADS)

    Farin, Maxime; Mangeney, Anne; de Rosny, Julien; Toussaint, Renaud; Trinh, Phuong-Thu

    2017-04-01

    Landslides, rock avalanche and debris flows represent a major natural hazard in steep environments. However, owing to the lack of visual observations, the dynamics of these gravitational events is still not well understood. A burning challenge is to deduce the landslide dynamics from the characteristics of the generated seismic signal. Laboratory experiments of granular columns collapse are conducted on an inclined plane. The seismic signal generated by the collapse is recorded by piezoelectric accelerometers sensitive in a wide frequency range (1 Hz - 56 kHz). The granular column is constituted with steel beads of same diameter that are initially contained in a cylinder. The column collapses when the cylinder is removed. A layer of steel beads is glued on the surface of the plane to provide basal roughness. We distinguish two successive phases of rise and decay in the seismic signal generated by the granular collapses. The rise phase of the seismic amplitude and its maximum are shown to be independent of the slope angle. The maximum seismic amplitude coincides with the maximum flow speed in the direction normal to the slope but not with the maximum downslope speed. The decay phase of the seismic amplitude lasts significantly longer as slope angle increases over a critical value. The decay becomes exponential for high slope angles > 15°. This change of signal shape on steep slopes seems to be related to the development of a different flow regime: a saltating front whose amplitude and duration also increase with slope angle. In addition, we propose a semi-empirical scaling law to describe how the seismic energy radiated by a granular flow increases when the slope angle increases. The fit of this law with the seismic data allows us to retrieve the friction angle of the granular material, which is a crucial rheological parameter. Finally, the conversion of the flows potential energy into radiated seismic energy is evaluated from 0.2% to 1%. It decreases as time

  12. Analysis of Signaling Endosome Composition and Dynamics Using SILAC in Embryonic Stem Cell-Derived Neurons*

    PubMed Central

    Debaisieux, Solène; Encheva, Vesela; Chakravarty, Probir; Snijders, Ambrosius P.; Schiavo, Giampietro

    2016-01-01

    Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics, and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and Gene Ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first

  13. Use of operational analyses to study the dynamics of troposphere-stratosphere interactions in polar regions

    NASA Technical Reports Server (NTRS)

    Salstein, David A.; Rosen, Richard D.; Miller, Alvin J.

    1988-01-01

    Operational analyses produced by large weather centers have been used in the past to monitor various aspects of the general circulation as well as address dynamical questions. For a number years researchers have been monitoring National Meteorological Center (NMC) analyses at 100 millibars because it is the level from which stratospheric analyses are built. In particular, they closely examined the pressure-work term at that level which is an important parameter related to the forcing of the stratosphere by the troposphere. Rapid fluctuations typically seen in this quanity during the months of July-November, and similarly noted by Randel et al., (1987) may raise some concern about the quality of the analyses. Researchers investigated the behavior of the term mainly responsible for these variations, namely the eddy flux of heat, and furthermore have corroborated the presence of these variations in contemporaneous analyses produced by the European Centre for Medium Range Forecasts (ECMWF). Researchers demonstrated that fluctuations in standing eddy heat fluxes, related to the forcing of the stratosphere by the troposphere, agree in two largely independent meteorological analyses. Researchers believe, that these fluctuations are mostly real.

  14. Quick and inexpensive paraffin-embedding method for dynamic bone formation analyses

    PubMed Central

    Porter, Amy; Irwin, Regina; Miller, Josselyn; Horan, Daniel J.; Robling, Alexander G.; McCabe, Laura R.

    2017-01-01

    We have developed a straightforward method that uses paraffin-embedded bone for undemineralized thin sectioning, which is amenable to subsequent dynamic bone formation measurements. Bone has stiffer material properties than paraffin, and therefore has hereforto usually been embedded in plastic blocks, cured and sectioned with a tungsten carbide knife to obtain mineralized bone sections for dynamic bone formation measures. This process is expensive and requires special equipment, experienced personnel, and time for the plastic to penetrate the bone and cure. Our method utilizes a novel way to prepare mineralized bone that increases its compliance so that it can be embedded and easily section in paraffin blocks. The approach is simple, quick, and costs less than 10% of the price for plastic embedded bone sections. While not effective for static bone measures, this method allows dynamic bone analyses to be readily performed in laboratories worldwide which might not otherwise have access to traditional (plastic) equipment and expertise. PMID:28198415

  15. On signals of phase transitions in salmon population dynamics

    PubMed Central

    Krkošek, Martin; Drake, John M.

    2014-01-01

    Critical slowing down (CSD) reflects the decline in resilience of equilibria near a bifurcation and may reveal early warning signals (EWS) of ecological phase transitions. We studied CSD in the recruitment dynamics of 120 stocks of three Pacific salmon (Oncorhynchus spp.) species in relation to critical transitions in fishery models. Pink salmon (Oncorhynchus gorbuscha) exhibited increased variability and autocorrelation in populations that had a growth parameter, r, close to zero, consistent with EWS of extinction. However, models and data for sockeye salmon (Oncorhynchus nerka) indicate that portfolio effects from heterogeneity in age-at-maturity may obscure EWS. Chum salmon (Oncorhynchus keta) show intermediate results. The data do not reveal EWS of Ricker-type bifurcations that cause oscillations and chaos at high r. These results not only provide empirical support for CSD in some ecological systems, but also indicate that portfolio effects of age structure may conceal EWS of some critical transitions. PMID:24759855

  16. Design of experiments to investigate dynamic cell signaling models.

    PubMed

    Bandara, Samuel; Meyer, Tobias

    2012-01-01

    This chapter describes approaches to make use of dynamic models of cell signaling systems in order to optimize experiments in cell biology. We are particularly focusing on the question of how small molecule inhibitors or activators can best be used to get the most information out of a limited number of experiments when only a handful of molecular species can be measured. One goal addressed by this chapter is to find time course experiments to discriminate between rivaling molecular mechanisms. The other goal is to find experiments that are useful for inferring rate constants, binding affinities, concentrations, and other model parameters from time course data. Both are treated as optimal control problems in which rapid pharmacological perturbation schemes are identified in silico in order to close an experimental cycle from modeling back to the laboratory bench.

  17. Dynamic time warping and machine learning for signal quality assessment of pulsatile signals.

    PubMed

    Li, Q; Clifford, G D

    2012-09-01

    In this work, we describe a beat-by-beat method for assessing the clinical utility of pulsatile waveforms, primarily recorded from cardiovascular blood volume or pressure changes, concentrating on the photoplethysmogram (PPG). Physiological blood flow is nonstationary, with pulses changing in height, width and morphology due to changes in heart rate, cardiac output, sensor type and hardware or software pre-processing requirements. Moreover, considerable inter-individual and sensor-location variability exists. Simple template matching methods are therefore inappropriate, and a patient-specific adaptive initialization is therefore required. We introduce dynamic time warping to stretch each beat to match a running template and combine it with several other features related to signal quality, including correlation and the percentage of the beat that appeared to be clipped. The features were then presented to a multi-layer perceptron neural network to learn the relationships between the parameters in the presence of good- and bad-quality pulses. An expert-labeled database of 1055 segments of PPG, each 6 s long, recorded from 104 separate critical care admissions during both normal and verified arrhythmic events, was used to train and test our algorithms. An accuracy of 97.5% on the training set and 95.2% on test set was found. The algorithm could be deployed as a stand-alone signal quality assessment algorithm for vetting the clinical utility of PPG traces or any similar quasi-periodic signal.

  18. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

    PubMed Central

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-01-01

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation. PMID:28223697

  19. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.

    PubMed

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-02-22

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.

  20. Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory

    NASA Astrophysics Data System (ADS)

    Tewatia, D. K.; Tolakanahalli, R. P.; Paliwal, B. R.; Tomé, W. A.

    2011-04-01

    The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

  1. Static and dynamic stress analyses of the prototype high head Francis runner based on site measurement

    NASA Astrophysics Data System (ADS)

    Huang, X.; Oram, C.; Sick, M.

    2014-03-01

    More efforts are put on hydro-power to balance voltage and frequency within seconds for primary control in modern smart grids. This requires hydraulic turbines to run at off-design conditions. especially at low load or speed-no load. Besides. the tendency of increasing power output and decreasing weight of the turbine runners has also led to the high level vibration problem of the runners. especially high head Francis runners. Therefore. it is important to carry out the static and dynamic stress analyses of prototype high head Francis runners. This paper investigates the static and dynamic stresses on the prototype high head Francis runner based on site measurements and numerical simulations. The site measurements are performed with pressure transducers and strain gauges. Based on the measured results. computational fluid dynamics (CFD) simulations for the flow channel from stay vane to draft tube cone are performed. Static pressure distributions and dynamic pressure pulsations caused by rotor-stator interaction (RSI) are obtained under various operating conditions. With the CFD results. static and dynamic stresses on the runner at different operating points are calculated by means of the finite element method (FEM). The agreement between simulation and measurement is analysed with linear regression method. which indicates that the numerical result agrees well with that of measurement. Furthermore. the maximum static and dynamic stresses on the runner blade are obtained at various operating points. The relations of the maximum stresses and the power output are discussed in detail. The influences of the boundary conditions on the structural behaviour of the runner are also discussed.

  2. Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling.

    PubMed

    Min, Le; Soltis, Kathleen; Reis, Ana Claudia S; Xu, Shuyun; Kuohung, Wendy; Jain, Manisha; Carroll, Rona S; Kaiser, Ursula B

    2014-01-01

    Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1-7 cells expressing KISS1R resulted in a biphasic increase in intracellular Ca(2+) ([Ca(2+)]i), with a rapid acute increase followed by a more sustained second phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled receptor, resulted in a much smaller second-phase [Ca(2+)]i response. The KISS1R-mediated second-phase [Ca(2+)]i response was abolished by removal of kisspeptin from cell culture medium. Notably, the second-phase [Ca(2+)]i response was also inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit receptor internalization and recycling, suggesting that KISS1R trafficking contributes to the sustained [Ca(2+)]i response. We further demonstrated that KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next investigated the fate of the internalized kisspeptin-KISS1R complex. Most internalized kisspeptin was released extracellularly in degraded form within 1 hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex. Using a biotinylation assay, we demonstrated that degradation of cell surface KISS1R was much slower than that of the internalized ligand, suggesting dissociated processing of the internalized kisspeptin-KISS1R complex. Taken together, our results suggest that the sustained calcium response to kisspeptin is dependent on the continued presence of extracellular ligand and is the result of dynamic KISS1R trafficking.

  3. Single-Cell Analyses Reveal That KISS1R-Expressing Cells Undergo Sustained Kisspeptin-Induced Signaling That Is Dependent upon An Influx of Extracellular Ca2+

    PubMed Central

    Pampillo, Macarena; Min, Le; Kaiser, Ursula B.; Bhattacharya, Moshmi

    2012-01-01

    The kisspeptin receptor (KISS1R) is a Gαq/11-coupled seven-transmembrane receptor activated by a group of peptides referred to as kisspeptins (Kps). The Kp/KISS1R signaling system is a powerful regulator of GnRH secretion, and inactivating mutations in this system are associated with hypogonadotropic hypogonadism. A recent study revealed that Kp triggers prolonged signaling; not from the inability of the receptor to undergo rapid desensitization, but instead from the maintenance of a dynamic and active pool of KISS1R at the cell surface. To investigate this further, we hypothesized that if a dynamic pool of receptor is maintained at the cell surface for a protracted period, chronic Kp-10 treatment would trigger the sustained activation of Gαq/11 as evidenced through the prolonged activation of phospholipase C, protein kinase C, and prolonged mobilization of intracellular Ca2+. Through single-cell analyses, we tested our hypothesis in human embryonic kidney (HEK) 293 cells and found that was indeed the case. We subsequently determined that prolonged KISS1R signaling was not a phenomenon specific to HEK 293 cells but is likely a conserved property of KISS1R-expressing cells because evidence of sustained KISS1R signaling was also observed in the GT1–7 GnRH neuronal and Chinese hamster ovary cell lines. While exploring the regulation of prolonged KISS1R signaling, we identified a critical role for extracellular Ca2+. We found that although free intracellular Ca2+, primarily derived from intracellular stores, was sufficient to trigger the acute activation of a major KISS1R secondary effector, protein kinase C, it was insufficient to sustain chronic KISS1R signaling; instead extracellular Ca2+ was absolutely required for this. PMID:23070548

  4. A bead-based western for high-throughput cellular signal transduction analyses

    PubMed Central

    Treindl, Fridolin; Ruprecht, Benjamin; Beiter, Yvonne; Schultz, Silke; Döttinger, Anette; Staebler, Annette; Joos, Thomas O.; Kling, Simon; Poetz, Oliver; Fehm, Tanja; Neubauer, Hans; Kuster, Bernhard; Templin, Markus F.

    2016-01-01

    Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes. PMID:27659302

  5. Dynamic protein interaction networks and new structural paradigms in signaling

    PubMed Central

    Csizmok, Veronika; Follis, Ariele Viacava; Kriwacki, Richard W.; Forman-Kay, Julie D.

    2017-01-01

    Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins and regions (IDPs/IDRs), which represent ~30% of the proteome and enable unique regulatory mechanisms. In this review we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as “ultrasensitivity” and “regulated folding and unfolding”. We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information. PMID:26922996

  6. Nuclear proton dynamics and interactions with calcium signaling.

    PubMed

    Hulikova, Alzbeta; Swietach, Pawel

    2016-07-01

    Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pHnuc), and how these could be exploited to control gene expression. Here, we show that pHnuc dynamics can be imaged using the DNA-binding dye Hoechst 33342. Nuclear pores allow the passage of medium-sized molecules (calcein), but protons must first bind to mobile buffers in order to gain access to the nucleoplasm. Fixed buffering residing in the nucleus of permeabilized cells was estimated to be very weak on the basis of the large amplitude of pHnuc transients evoked by photolytic H(+)-uncaging or exposure to weak acids/bases. Consequently, the majority of nuclear pH buffering is sourced from the cytoplasm in the form of mobile buffers. Effective proton diffusion was faster in nucleoplasm than in cytoplasm, in agreement with the higher mobile-to-fixed buffering ratio in the nucleus. Cardiac myocyte pHnuc changed in response to maneuvers that alter nuclear Ca(2+) signals. Blocking Ca(2+) release from inositol-1,4,5-trisphosphate receptors stably alkalinized the nucleus. This Ca(2+)-pH interaction may arise from competitive binding to common chemical moieties. Competitive binding to mobile buffers may couple the efflux of Ca(2+)via nuclear pores with a counterflux of protons. This would generate a stable pH gradient between cytoplasm and nucleus that is sensitive to the state of nuclear Ca(2+) signaling. The unusual behavior of protons in the nucleus provides new mechanisms for regulating cardiac nuclear biology. Copyright © 2015. Published by Elsevier Ltd.

  7. Dynamic conformal arc therapy: Transmitted signal in vivo dosimetry

    SciTech Connect

    Piermattei, Angelo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando Maria; Cellini, Francesco; Trodella, Lucio; D'Onofrio, Guido; Grimaldi, Luca; Cilla, Savino; Fidanzio, Andrea; Placidi, Elisa; Azario, Luigi

    2008-05-15

    A method for the determination of the in vivo isocenter dose, D{sub iso}, has been applied to the dynamic conformal arc therapy (DCAT) for thoracic tumors. The method makes use of the transmitted signal, S{sub t,{alpha}}, measured at different gantry angles, {alpha}, by a small ion chamber positioned on the electronic portal imaging device. The in vivo method is implemented by a set of correlation functions obtained by the ratios between the transmitted signal and the midplane dose in a solid phantom, irradiated by static fields. The in vivo dosimetry at the isocenter for the DCAT requires the convolution between the signals , S{sub t,{alpha}}, and the dose reconstruction factors, C{sub {alpha}}, that depend on the patient's anatomy and on its tissue inhomogeneities along the beam central axis in the {alpha} direction. The C{sub {alpha}} factors are obtained by processing the patient's computed tomography scan. The method was tested by taking measurements in a cylindrical phantom and in a Rando Alderson phantom. The results show that the difference between the convolution calculations and the phantom measurements is within {+-}2%. The in vivo dosimetry of the stereotactic DCAT for six lung tumors, irradiated with three or four arcs, is reported. The isocenter dose up to 17 Gy per therapy fraction was delivered on alternating days for three fractions. The agreement obtained in this pilot study between the total in vivo dose D{sub iso} and the planned dose D{sub iso,TPS} at the isocenter is {+-}4%. The method has been applied on the DCAT obtaining a more extensive monitoring of possible systematic errors, the effect of which can invalidate the current therapy which uses a few high-dose fractions.

  8. Direct observation of the dynamic process underlying allosteric signal transmission.

    PubMed

    Brüschweiler, Sven; Schanda, Paul; Kloiber, Karin; Brutscher, Bernhard; Kontaxis, Georg; Konrat, Robert; Tollinger, Martin

    2009-03-04

    Allosteric regulation is an effective mechanism of control in biological processes. In allosteric proteins a signal originating at one site in the molecule is communicated through the protein structure to trigger a specific response at a remote site. Using NMR relaxation dispersion techniques we directly observe the dynamic process through which the KIX domain of CREB binding protein communicates allosteric information between binding sites. KIX mediates cooperativity between pairs of transcription factors through binding to two distinct interaction surfaces in an allosteric manner. We show that binding the activation domain of the mixed lineage leukemia (MLL) transcription factor to KIX induces a redistribution of the relative populations of KIX conformations toward a high-energy state in which the allosterically activated second binding site is already preformed, consistent with the Monod-Wyman-Changeux (WMC) model of allostery. The structural rearrangement process that links the two conformers and by which allosteric information is communicated occurs with a time constant of 3 ms at 27 degrees C. Our dynamic NMR data reveal that an evolutionarily conserved network of hydrophobic amino acids constitutes the pathway through which information is transmitted.

  9. On the role of subthreshold dynamics in neuronal signaling.

    PubMed

    Clay, J R; Shrier, A

    1999-03-21

    The role of subthreshold dynamics in neuronal signaling is examined using periodic pulse train stimulation of the Fitzhugh-Nagumo (FN) model of nerve membrane excitability and results from the squid giant axon as an experimental data base. For a broad range of stimulus conditions the first pulse in a pulse train elicited an action potential, whereas all subsequent pulses elicited subthreshold responses, both in the axon and in the FN model. These results are not well described by the Hodgkin and Huxley 1952 model. Various different patterns of subthreshold responses, including chaotic dynamics, can be observed in both systems-the FN model and the axon-depending upon stimulus conditions. For some conditions action potentials are occasionally interspersed among the subthreshold events with randomly occurring interspike intervals. The randomness is directly attributable to the underlying subthreshold chaos-deterministic chaos-rather than to a stochastic noise source. We conclude that this mechanism may contribute to multimodal interspike interval histograms which have been observed from individual neurons throughout the nervous system. Copyright 1999 Academic Press.

  10. Analysing animal social network dynamics: the potential of stochastic actor-oriented models.

    PubMed

    Fisher, David N; Ilany, Amiyaal; Silk, Matthew J; Tregenza, Tom

    2017-03-01

    Animals are embedded in dynamically changing networks of relationships with conspecifics. These dynamic networks are fundamental aspects of their environment, creating selection on behaviours and other traits. However, most social network-based approaches in ecology are constrained to considering networks as static, despite several calls for such analyses to become more dynamic. There are a number of statistical analyses developed in the social sciences that are increasingly being applied to animal networks, of which stochastic actor-oriented models (SAOMs) are a principal example. SAOMs are a class of individual-based models designed to model transitions in networks between discrete time points, as influenced by network structure and covariates. It is not clear, however, how useful such techniques are to ecologists, and whether they are suited to animal social networks. We review the recent applications of SAOMs to animal networks, outlining findings and assessing the strengths and weaknesses of SAOMs when applied to animal rather than human networks. We go on to highlight the types of ecological and evolutionary processes that SAOMs can be used to study. SAOMs can include effects and covariates for individuals, dyads and populations, which can be constant or variable. This allows for the examination of a wide range of questions of interest to ecologists. However, high-resolution data are required, meaning SAOMs will not be useable in all study systems. It remains unclear how robust SAOMs are to missing data and uncertainty around social relationships. Ultimately, we encourage the careful application of SAOMs in appropriate systems, with dynamic network analyses likely to prove highly informative. Researchers can then extend the basic method to tackle a range of existing questions in ecology and explore novel lines of questioning. © 2016 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

  11. Variational Assimilation of Global Microwave Rainfall Retrievals: Physical and Dynamical Impact on GEOS Analyses and Forecasts

    NASA Technical Reports Server (NTRS)

    Lin, Xin; Zhang, Sara Q.; Hou, Arthur Y.

    2006-01-01

    Global microwave rainfall retrievals from a 5-satellite constellation, including TMI from TRMM, SSWI from DMSP F13, F14 and F15, and AMSR-E from EOS-AQUA, are assimilated into the NASA Goddard Earth Observing System (GEOS) Data Assimilation System (DAS) using a 1-D variational continuous assimilation (VCA) algorithm. The physical and dynamical impact of rainfall assimilation on GEOS analyses and forecasts is examined at various temporal and spatial scales. This study demonstrates that the 1-D VCA algorithm, which was originally developed and evaluated for rainfall assimilations over tropical oceans, can effectively assimilate satellite microwave rainfall retrievals and improve GEOS analyses over both the Tropics and the extratropics where the atmospheric processes are dominated by different large-scale dynamics and moist physics, and also over the land, where rainfall estimates from passive microwave radiometers are believed to be less accurate. Results show that rainfall assimilation renders the GEOS analysis physically and dynamically more consistent with the observed precipitation at the monthly-mean and 6-hour time scales. Over regions where the model precipitation tends to misbehave in distinctly different rainy regimes, the 1-D VCA algorithm, by compensating for errors in the model s moist time-tendency in a 6-h analysis window, is able to bring the rainfall analysis closer to the observed. The radiation and cloud fields also tend to be in better agreement with independent satellite observations in the rainfall-assimilation m especially over regions where rainfall analyses indicate large improvements. Assimilation experiments with and without rainfall data for a midlatitude frontal system clearly indicates that the GEOS analysis is improved through changes in the thermodynamic and dynamic fields that respond to the rainfall assimilation. The synoptic structures of temperature, moisture, winds, divergence, and vertical motion, as well as vorticity are more

  12. Observation of Wetland Dynamics with Global Navigation Satellite Signals Reflectometry

    NASA Astrophysics Data System (ADS)

    Zuffada, C.; Shah, R.; Nghiem, S. V.; Cardellach, E.; Chew, C. C.

    2015-12-01

    Wetland dynamics is crucial to changes in both atmospheric methane and terrestrial water storage. The Intergovernmental Panel on Climate Change's Fifth Assessment Report (IPCC AR5) highlights the role of wetlands as a key driver of methane (CH4) emission, which is more than one order of magnitude stronger than carbon dioxide as a greenhouse gas in the centennial time scale. Among the multitude of methane emission sources (hydrates, livestock, rice cultivation, freshwaters, landfills and waste, fossil fuels, biomass burning, termites, geological sources, and soil oxidation), wetlands constitute the largest contributor with the widest uncertainty range of 177-284 Tg(CH4) yr-1 according to the IPCC estimate. Wetlands are highly susceptible to climate change that might lead to wetland collapse. Such wetland destruction would decrease the terrestrial water storage capacity and thus contribute to sea level rise, consequently exacerbating coastal flooding problems. For both methane change and water storage change, wetland dynamics is a crucial factor with the largest uncertainty. Nevertheless, a complete and consistent map of global wetlands still needs to be obtained as the Ramsar Convention calls for a wetlands inventory and impact assessment. We develop a new method for observations of wetland change using Global Navigation Satellite Signals Reflectometry (GNSS-R) signatures for global wetland mapping in synergy with the existing capability, not only as a static inventory but also as a temporal dataset, to advance the capability for monitoring the dynamics of wetland extent relevant to addressing the science issues of CH4 emission change and terrestrial water storage change. We will demonstrate the capability of the new GNSS-R method over a rice field in the Ebro Delta wetland in Spain.

  13. Regulation of neuronal PKA signaling through AKAP targeting dynamics.

    PubMed

    Dell'Acqua, Mark L; Smith, Karen E; Gorski, Jessica A; Horne, Eric A; Gibson, Emily S; Gomez, Lisa L

    2006-07-01

    region that binds phosphatidylinositol-4,5-bisphosphate (PIP(2)), F-actin, and actin-linked cadherin adhesion molecules. Thus, anchoring of PKA and CaN as well as physical linkage of the AKAP to both cadherin-cytoskeletal and MAGUK-receptor complexes could play roles in coordinating changes in synaptic structure and receptor signaling functions underlying plasticity. Importantly, we provide evidence showing that NMDAR-CaN signaling pathways implicated in AMPAR regulation during LTD lead to a disruption of AKAP79/150 interactions with actin, MAGUKs, and cadherins and lead to a loss of the AKAP and anchored PKA from postsynapses. Our studies thus far indicate that this AKAP79/150 translocation depends on activation of CaN, F-actin reorganization, and possibly Ca(2+)-CaM binding to the N-terminal basic regions. Importantly, this tranlocation of the AKAP79/150-PKA complex from spines may shift the balance of PKA kinase and CaN/PP1 phosphatase activity at the postsynapse in favor of the phosphatases. This loss of PKA could then promote actions of CaN and PP1 during induction of LTD including maintaining AMPAR dephosphorylation, promoting AMPAR endocytosis, and preventing AMPAR recycling. Overall, these findings challenge the accepted notion that AKAPs are static anchors that position signaling proteins near fixed target substrates and instead suggest that AKAPs can function in more dynamic manners to regulate local signaling events.

  14. Development of microbial-enzyme-mediated decomposition model parameters through steady-state and dynamic analyses

    SciTech Connect

    Wang, Gangsheng; Post, Wilfred M; Mayes, Melanie

    2013-01-01

    We developed a Microbial-ENzyme-mediated Decomposition (MEND) model, based on the Michaelis-Menten kinetics, that describes the dynamics of physically defined pools of soil organic matter (SOC). These include particulate, mineral-associated, dissolved organic matter (POC, MOC, and DOC, respectively), microbial biomass, and associated exoenzymes. The ranges and/or distributions of parameters were determined by both analytical steady-state and dynamic analyses with SOC data from the literature. We used an improved multi-objective parameter sensitivity analysis (MOPSA) to identify the most important parameters for the full model: maintenance of microbial biomass, turnover and synthesis of enzymes, and carbon use efficiency (CUE). The model predicted an increase of 2 C (baseline temperature =12 C) caused the pools of POC-Cellulose, MOC, and total SOC to increase with dynamic CUE and decrease with constant CUE, as indicated by the 50% confidence intervals. Regardless of dynamic or constant CUE, the pool sizes of POC, MOC, and total SOC varied from 8% to 8% under +2 C. The scenario analysis using a single parameter set indicates that higher temperature with dynamic CUE might result in greater net increases in both POC-Cellulose and MOC pools. Different dynamics of various SOC pools reflected the catalytic functions of specific enzymes targeting specific substrates and the interactions between microbes, enzymes, and SOC. With the feasible parameter values estimated in this study, models incorporating fundamental principles of microbial-enzyme dynamics can lead to simulation results qualitatively different from traditional models with fast/slow/passive pools.

  15. Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

    SciTech Connect

    YANG, CHIN-RANG

    2013-12-11

    Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complement Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.

  16. Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings.

    PubMed

    Otaki, Joji M

    2012-03-13

    To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly Junonia almana. In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to butterfly eyespots, delineates a theoretical basis for the

  17. Dynamics, stability, and control analyses of flapping wing micro-air vehicles

    NASA Astrophysics Data System (ADS)

    Orlowski, Christopher T.; Girard, Anouck R.

    2012-05-01

    The paper presents an overview of the various analyses of flight dynamics, stability, and control of flapping wing micro-air vehicles available in the literature. The potential benefits of flapping wing micro-air vehicles for civil, military, and search and rescue operations are numerous. The majority of the flight dynamics research involves the standard aircraft (6DOF) equations of motion, although a growth is evident in examining the multibody flight dynamics models of flapping wing micro-air vehicles. The stability of flapping wing micro-air vehicles is largely studied in the vicinity of hover and forward flight. The majority of stability studies focus on linear, time-invariant stability in the vicinity of reference flight conditions, such as hover or forward flight. The consistent result is that flapping wing micro-air vehicles are unstable in an open loop setting. The unstable result is based on linear and nonlinear stability analyses. Control has been demonstrated for hovering and forward flight through various methods, both linear and nonlinear in nature. The entirety of reported research into the stability and control of flapping wing micro-air vehicles has neglected the mass effects of the wings on the position and orientation of the central body. Successful control of a flapping wing micro-air vehicle, with the wings' mass effects included, is still an open research area.

  18. Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling.

    PubMed

    Hardeland, Rüdiger; Madrid, Juan Antonio; Tan, Dun-Xian; Reiter, Russel J

    2012-03-01

    Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

  19. An Interactive Macrophage Signal Transduction Map Facilitates Comparative Analyses of High-Throughput Data.

    PubMed

    Wentker, Pia; Eberhardt, Martin; Dreyer, Florian S; Bertrams, Wilhelm; Cantone, Martina; Griss, Kathrin; Schmeck, Bernd; Vera, Julio

    2017-03-01

    Macrophages (Mϕs) are key players in the coordination of the lifesaving or detrimental immune response against infections. The mechanistic understanding of the functional modulation of Mϕs by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. The complexity of pathways and their cross-talk benefits from holistic computational approaches. In the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction pathways in inflammatory Mϕs based on the current literature. In a second step, we selectively expanded this curated map with database knowledge. We provide both versions to the scientific community via a Web platform that is designed to facilitate exploration and analysis of high-throughput data. The platform comes preloaded with logarithmic fold changes from 44 data sets on Mϕ stimulation. We exploited three of these data sets-human primary Mϕs infected with the common lung pathogens Streptococcus pneumoniae, Legionella pneumophila, or Mycobacterium tuberculosis-in a case study to show how our map can be customized with expression data to pinpoint regulated subnetworks and druggable molecules. From the three infection scenarios, we extracted a regulatory core of 41 factors, including TNF, CCL5, CXCL10, IL-18, and IL-12 p40, and identified 140 drugs targeting 16 of them. Our approach promotes a comprehensive systems biology strategy for the exploitation of high-throughput data in the context of Mϕ signal transduction. In conclusion, we provide a set of tools to help scientists unravel details of Mϕ signaling. The interactive version of our Mϕ signal transduction map is accessible online at https://vcells.net/macrophage. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. Analysing and controlling the tax evasion dynamics via majority-vote model

    NASA Astrophysics Data System (ADS)

    Lima, F. W. S.

    2010-09-01

    Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on simple square lattices, Voronoi-Delaunay random lattices, Barabasi-Albert networks, and Erdös-Rényi random graphs. In the order to analyse and to control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhod of the noise critical qc to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies cited above giving the same behavior regardless of dynamic or topology used here.

  1. Static and dynamic theoretical analyses of a scanning tip on suspended graphene surface

    NASA Astrophysics Data System (ADS)

    Yu, Yan-Zi; Guo, Jian-Gang

    2016-08-01

    Recent research progress shows that graphene exhibits distinct adhesion and friction behaviors. In the paper, the static and dynamic analyses of a diamond tip sliding on suspended graphene surface are conducted via theoretical and numerical research methods, and the adhesion and friction properties between them are investigated. The analytical expression of interaction potential between a diamond tip and graphene surface is derived based on the interatomic pairwise potential, and then, the lateral and normal interaction forces are calculated. The equilibrium heights and adhesion energy of the diamond tip are calculated on three particular sites of graphene surface. The influence of vertical distance between the tip and graphene surface is studied on the maximum static frictional force and initial velocity of tip. What is more, the influence of scanning velocity and damping are also analyzed on the frictional force and dynamic behaviors of the scanning tip, and the "stick-slip" phenomenon is observed and discussed by the numerical calculation.

  2. Prediction of Seismic Slope Displacements by Dynamic Stick-Slip Analyses

    SciTech Connect

    Ausilio, Ernesto; Costanzo, Antonio; Silvestri, Francesco; Tropeano, Giuseppe

    2008-07-08

    A good-working balance between simplicity and reliability in assessing seismic slope stability is represented by displacement-based methods, in which the effects of deformability and ductility can be either decoupled or coupled in the dynamic analyses. In this paper, a 1D lumped mass 'stick-slip' model is developed, accounting for soil heterogeneity and non-linear behaviour, with a base sliding mechanism at a potential rupture surface. The results of the preliminary calibration show a good agreement with frequency-domain site response analysis in no-slip conditions. The comparison with rigid sliding block analyses and with the decoupled approach proves that the stick-slip procedure can result increasingly unconservative for soft soils and deep sliding depths.

  3. Dynamic Interpretation of Hedgehog Signaling in the Drosophila Wing Disc

    PubMed Central

    Nahmad, Marcos; Stathopoulos, Angelike

    2009-01-01

    Morphogens are classically defined as molecules that control patterning by acting at a distance to regulate gene expression in a concentration-dependent manner. In the Drosophila wing imaginal disc, secreted Hedgehog (Hh) forms an extracellular gradient that organizes patterning along the anterior–posterior axis and specifies at least three different domains of gene expression. Although the prevailing view is that Hh functions in the Drosophila wing disc as a classical morphogen, a direct correspondence between the borders of these patterns and Hh concentration thresholds has not been demonstrated. Here, we provide evidence that the interpretation of Hh signaling depends on the history of exposure to Hh and propose that a single concentration threshold is sufficient to support multiple outputs. Using mathematical modeling, we predict that at steady state, only two domains can be defined in response to Hh, suggesting that the boundaries of two or more gene expression patterns cannot be specified by a static Hh gradient. Computer simulations suggest that a spatial “overshoot” of the Hh gradient occurs, i.e., a transient state in which the Hh profile is expanded compared to the Hh steady-state gradient. Through a temporal examination of Hh target gene expression, we observe that the patterns initially expand anteriorly and then refine, providing in vivo evidence for the overshoot. The Hh gene network architecture suggests this overshoot results from the Hh-dependent up-regulation of the receptor, Patched (Ptc). In fact, when the network structure was altered such that the ptc gene is no longer up-regulated in response to Hh-signaling activation, we found that the patterns of gene expression, which have distinct borders in wild-type discs, now overlap. Our results support a model in which Hh gradient dynamics, resulting from Ptc up-regulation, play an instructional role in the establishment of patterns of gene expression. PMID:19787036

  4. Spatial and temporal analyses of geothermal climate signals: Implications for borehole paleoclimatology

    NASA Astrophysics Data System (ADS)

    Smerdon, Jason E.

    Inversions of subsurface temperature profiles to reconstruct ground surface temperature (GST) histories have been widely used as indicators of paleoclimate. These reconstructions assume that heat transport within the subsurface is conductive. Climatic interpretations of GST reconstructions also assume that GST is strongly coupled to surface air temperature (SAT) on timescales of decades and longer. I examine these two assumptions using records of SAT and subsurface temperature time series from Fargo, North Dakota; Prague, Czech Republic; Cape Henlopen State Park, Delaware; and Cape Hatteras National Seashore, North Carolina. These records comprise intra-daily observations that span parts of one or two decades. The characteristics of downward-propagating annual temperature signals at each site clearly indicate that heat transport in the subsurface can be described as one-dimensional conduction in a homogeneous medium. Extrapolations of subsurface observations to the ground surface yield estimates of annual GST signals, and allow comparisons to annual SAT signals. All annual GST signals are modestly attenuated and negligibly phase shifted relative to SAT. Relationships between GST and SAT are further explored on daily, seasonal, and annual timescales to identify and characterize the principal meteorological factors that lead to differences between GST and SAT. I compare subsurface temperature observations to calculations from a conductive subsurface model driven with daily SAT as the surface boundary condition and show daily differences exist between observed and modeled subsurface temperatures. Year-to-year spectral decompositions of daily SAT and subsurface temperature time series are also analyzed. Dissimilarities exist between annual amplitudes of GST and SAT signals. These amplitude differences partition into summer and winter seasons and can lead to mean annual GST that is either cooler or warmer than SAT. Additionally, the differences between mean annual GST

  5. Evolutionary dynamics of influenza A nucleoprotein (NP) lineages revealed by large-scale sequence analyses.

    PubMed

    Xu, Jianpeng; Christman, Mary C; Donis, Ruben O; Lu, Guoqing

    2011-12-01

    Influenza A viral nucleoprotein (NP) plays a critical role in virus replication and host adaptation, however, the underlying molecular evolutionary dynamics of NP lineages are less well-understood. In this study, large-scale analyses of 5094 NP nucleotide sequences revealed eight distinct evolutionary lineages, including three host-specific lineages (human, classical swine and equine), two cross-host lineages (Eurasian avian-like swine and swine-origin human pandemic H1N1 2009) and three geographically isolated avian lineages (Eurasian, North American and Oceanian). The average nucleotide substitution rate of the NP lineages was estimated to be 2.4 × 10(-3) substitutions per site per year, with the highest value observed in pandemic H1N1 2009 (3.4 × 10(-3)) and the lowest in equine (0.9 × 10(-3)). The estimated time of most recent common ancestor (TMRCA) for each lineage demonstrated that the earliest human lineage was derived around 1906, and the latest pandemic H1N1 2009 lineage dated back to December 17, 2008. A marked time gap was found between the times when the viruses emerged and were first sampled, suggesting the crucial role for long-term surveillance of newly emerging viruses. The selection analyses showed that human lineage had six positive selection sites, whereas pandemic H1N1 2009, classical swine, Eurasian avian and Eurasian swine had only one or two sites. Protein structure analyses revealed several positive selection sites located in epitope regions or host adaptation regions, indicating strong adaptation to host immune system pressures in influenza viruses. Along with previous studies, this study provides new insights into the evolutionary dynamics of influenza A NP lineages. Further lineage analyses of other gene segments will allow better understanding of influenza A virus evolution and assist in the improvement of global influenza surveillance.

  6. Signal-Detection Analyses of Conditional Discrimination and Delayed Matching-to-Sample Performance

    ERIC Educational Resources Information Center

    Alsop, Brent

    2004-01-01

    Quantitative analyses of stimulus control and reinforcer control in conditional discriminations and delayed matching-to-sample procedures often encounter a problem; it is not clear how to analyze data when subjects have not made errors. The present article examines two common methods for overcoming this problem. Monte Carlo simulations of…

  7. ALISSA: an automated live-cell imaging system for signal transduction analyses.

    PubMed

    Wenus, Jakub; Düssmann, Heiko; Paul, Perrine; Kalamatianos, Dimitrios; Rehm, Markus; Wellstead, Peter; Prehn, Jochen; Huber, Heinrich

    2009-12-01

    Probe photobleaching and a specimen's sensitivity to phototoxicity severely limit the number of possible excitation cycles in time-lapse fluorescent microscopy experiments. Consequently, when a study of cellular processes requires measurements over hours or days, temporal resolution is limited, and spontaneous or rapid events may be missed, thus limiting conclusions about transduction events. We have developed ALISSA, a design framework and reference implementation for an automated live-cell imaging system for signal transduction analysis. It allows an adaptation of image modalities and laser resources tailored to the biological process, and thereby extends temporal resolution from minutes to seconds. The system employs online image analysis to detect cellular events that are then used to exercise microscope control. It consists of a reusable image analysis software for cell segmentation, tracking, and time series extraction, and a measurement-specific process control software that can be easily adapted to various biological settings. We have applied the ALISSA framework to the analysis of apoptosis as a demonstration case for slow onset and rapid execution signaling. The demonstration provides a clear proof-of-concept for ALISSA, and offers guidelines for its application in a broad spectrum of signal transduction studies.

  8. Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes.

    PubMed

    Brännmark, Cecilia; Nyman, Elin; Fagerholm, Siri; Bergenholm, Linnéa; Ekstrand, Eva-Maria; Cedersund, Gunnar; Strålfors, Peter

    2013-04-05

    Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems level mechanistic understanding of insulin resistance, using systems wide and internally consistent data from human adipocytes. Based on quantitative steady-state and dynamic time course data on signaling intermediaries, normally and in diabetes, we developed a dynamic mathematical model of insulin signaling. The model structure and parameters are identical in the normal and diabetic states of the model, except for three parameters that change in diabetes: (i) reduced concentration of insulin receptor, (ii) reduced concentration of insulin-regulated glucose transporter GLUT4, and (iii) changed feedback from mammalian target of rapamycin in complex with raptor (mTORC1). Modeling reveals that at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, which explains reduced sensitivity and signal strength throughout the signaling network. Model simulations with inhibition of mTORC1 are comparable with experimental data on inhibition of mTORC1 using rapamycin in human adipocytes. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling, both at the cellular level and, using a multilevel model, at the whole body level. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis.

  9. Interaction between telencephalic signals and respiratory dynamics in songbirds.

    PubMed

    Méndez, Jorge M; Mindlin, Gabriel B; Goller, Franz

    2012-06-01

    The mechanisms by which telencephalic areas affect motor activities are largely unknown. They could either take over motor control from downstream motor circuits or interact with the intrinsic dynamics of these circuits. Both models have been proposed for telencephalic control of respiration during learned vocal behavior in birds. The interactive model postulates that simple signals from the telencephalic song control areas are sufficient to drive the nonlinear respiratory network into producing complex temporal sequences. We tested this basic assumption by electrically stimulating telencephalic song control areas and analyzing the resulting respiratory patterns in zebra finches and in canaries. We found strong evidence for interaction between the rhythm of stimulation and the intrinsic respiratory rhythm, including naturally emerging subharmonic behavior and integration of lateralized telencephalic input. The evidence for clear interaction in our experimental paradigm suggests that telencephalic vocal control also uses a similar mechanism. Furthermore, species differences in the response of the respiratory system to stimulation show parallels to differences in the respiratory patterns of song, suggesting that the interactive production of respiratory rhythms is manifested in species-specific specialization of the involved circuitry.

  10. Cell cycle dynamics in a response/signalling feedback system with a gap.

    PubMed

    Gong, Xue; Buckalew, Richard; Young, Todd; Boczko, Erik

    2014-01-01

    We consider a dynamical model of cell cycles of n cells in a culture in which cells in one specific phase (S for signalling) of the cell cycle produce chemical agents that influence the growth/cell cycle progression of cells in another phase (R for responsive). In the case that the feedback is negative, it is known that subpopulations of cells tend to become clustered in the cell cycle; while for a positive feedback, all the cells tend to become synchronized. In this paper, we suppose that there is a gap between the two phases. The gap can be thought of as modelling the physical reality of a time delay in the production and action of the signalling agents. We completely analyse the dynamics of this system when the cells are arranged into two cell cycle clusters. We also consider the stability of certain important periodic solutions in which clusters of cells have a cyclic arrangement and there are just enough clusters to allow interactions between them. We find that the inclusion of a small gap does not greatly alter the global dynamics of the system; there are still large open sets of parameters for which clustered solutions are stable. Thus, we add to the evidence that clustering can be a robust phenomenon in biological systems. However, the gap does effect the system by enhancing the stability of the stable clustered solutions. We explain this phenomenon in terms of contraction rates (Floquet exponents) in various invariant subspaces of the system. We conclude that in systems for which these models are reasonable, a delay in signalling is advantageous to the emergence of clustering.

  11. GNA15 expression in small intestinal neuroendocrine neoplasia: functional and signalling pathway analyses.

    PubMed

    Zanini, Sara; Giovinazzo, Francesco; Alaimo, Daniele; Lawrence, Ben; Pfragner, Roswitha; Bassi, Claudio; Modlin, Irvin; Kidd, Mark

    2015-05-01

    Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) comprises a heterogeneous group of tumours that exhibit widely divergent biological behaviour. The identification of new targetable GPCR-pathways involved in regulating cell function could help to identify new therapeutic strategies. We assessed the function of a haematopoietic stem cell heterotrimeric G-protein, Gα15, in gut neuroendocrine cell models and examined the clinical implications of its over expression. Functional assays were undertaken to define the role of GNA15 in the small intestinal NEN cell line KRJ-I and in clinical samples from small intestinal NENs using quantitative polymerase chain reaction, western blot, proliferation and apoptosis assays, immunoprecipitation, immunohistochemistry (IHC) and automated quantitative analysis (AQUA). GNA15 was not expressed in normal neuroendocrine cells but was overexpressed in GEP-NEN cell lines. In KRJ-I cells, decreased expression of GNA15 was associated with inhibition of proliferation, activation of apoptosis and differential effects on pro-proliferative ERK, NFκB and Akt pathway signalling. Moreover, Gα15 was demonstrated to couple to the ß1 adrenergic receptor and modulated proliferative signals through this GPCR. Transcript and protein levels of GNA15 were significantly elevated in primary and metastatic tumours compared to normal mucosa and were particularly increased in low Ki-67 expressing tumours. IHC and AQUA revealed that a higher Gα15 expression was associated with a poorer survival. GNA15 may have a pathobiological role in SI-NENs. Targeting this signalling mediator could provide an opportunity for the development of new therapeutic strategies for this tumour type. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Dynamics and spatial structure of ENSO from re-analyses versus CMIP5 models

    NASA Astrophysics Data System (ADS)

    Serykh, Ilya; Sonechkin, Dmitry

    2016-04-01

    Basing on a mathematical idea about the so-called strange nonchaotic attractor (SNA) in the quasi-periodically forced dynamical systems, the currently available re-analyses data are considered. It is found that the El Niño - Southern Oscillation (ENSO) is driven not only by the seasonal heating, but also by three more external periodicities (incommensurate to the annual period) associated with the ~18.6-year lunar-solar nutation of the Earth rotation axis, ~11-year sunspot activity cycle and the ~14-month Chandler wobble in the Earth's pole motion. Because of the incommensurability of their periods all four forces affect the system in inappropriate time moments. As a result, the ENSO time series look to be very complex (strange in mathematical terms) but nonchaotic. The power spectra of ENSO indices reveal numerous peaks located at the periods that are multiples of the above periodicities as well as at their sub- and super-harmonic. In spite of the above ENSO complexity, a mutual order seems to be inherent to the ENSO time series and their spectra. This order reveals itself in the existence of a scaling of the power spectrum peaks and respective rhythms in the ENSO dynamics that look like the power spectrum and dynamics of the SNA. It means there are no limits to forecast ENSO, in principle. In practice, it opens a possibility to forecast ENSO for several years ahead. Global spatial structures of anomalies during El Niño and power spectra of ENSO indices from re-analyses are compared with the respective output quantities in the CMIP5 climate models (the Historical experiment). It is found that the models reproduce global spatial structures of the near surface temperature and sea level pressure anomalies during El Niño very similar to these fields in the re-analyses considered. But the power spectra of the ENSO indices from the CMIP5 models show no peaks at the same periods as the re-analyses power spectra. We suppose that it is possible to improve modeled

  13. Combined analytical and numerical approaches in Dynamic Stability analyses of engineering systems

    NASA Astrophysics Data System (ADS)

    Náprstek, Jiří

    2015-03-01

    Dynamic Stability is a widely studied area that has attracted many researchers from various disciplines. Although Dynamic Stability is usually associated with mechanics, theoretical physics or other natural and technical disciplines, it is also relevant to social, economic, and philosophical areas of our lives. Therefore, it is useful to occasionally highlight the general aspects of this amazing area, to present some relevant examples and to evaluate its position among the various branches of Rational Mechanics. From this perspective, the aim of this study is to present a brief review concerning the Dynamic Stability problem, its basic definitions and principles, important phenomena, research motivations and applications in engineering. The relationships with relevant systems that are prone to stability loss (encountered in other areas such as physics, other natural sciences and engineering) are also noted. The theoretical background, which is applicable to many disciplines, is presented. In this paper, the most frequently used Dynamic Stability analysis methods are presented in relation to individual dynamic systems that are widely discussed in various engineering branches. In particular, the Lyapunov function and exponent procedures, Routh-Hurwitz, Liénard, and other theorems are outlined together with demonstrations. The possibilities for analytical and numerical procedures are mentioned together with possible feedback from experimental research and testing. The strengths and shortcomings of these approaches are evaluated together with examples of their effective complementing of each other. The systems that are widely encountered in engineering are presented in the form of mathematical models. The analyses of their Dynamic Stability and post-critical behaviour are also presented. The stability limits, bifurcation points, quasi-periodic response processes and chaotic regimes are discussed. The limit cycle existence and stability are examined together with their

  14. Using stability analyses to predict dynamic behaviour of self-oscillating polymer gels

    NASA Astrophysics Data System (ADS)

    Palkar, Vaibhav; Srivastava, Gaurav; Kuksenok, Olga; Balazs, Anna C.; Dayal, Pratyush

    2015-03-01

    Use of chemo-mechanical transduction to produce locomotion is one of the significant characteristics of biological systems. Polymer gels, intrinsically powered by oscillatory Belousov-Zhabotinsky (BZ) reaction, are biomimetic materials that exhibit rhythmic self-sustained mechanical oscillations by chemo-mechanical transduction. Via simulations, based on the 3D gel lattice spring model, we have successfully captured the dynamic behaviour of BZ gels. We have demonstrated that it is possible to direct the movement of BZ gels along complex paths, guiding them to bend, reorient and turn. From a mathematical perspective, the oscillations in the BZ gels occur when the gel's steady states loose stability by virtue of Hopf bifurcations (HB). Through the use of stability analyses, we predict the conditions under which gel switches from stationary to oscillatory mode and vice versa. In addition, we characterize the nature of HB and also identify other types of bifurcations that play a critical role in governing the dynamic behaviour of BZ gels. Also, we successfully predict the frequency of chemo-mechanical oscillations and characterize its dependency on the model parameters. Our approach not only allows us to establish optimal conditions for the motion of BZ gels, but also can be used to design other dynamical systems. IIT Gandhinagar and DST-SERB for funding.

  15. STRUCTURAL ANALYSES OF FUEL CASKS SUBJECTED TO BOLT PRELOAD, INTERNAL PRESSURE AND SEQUENTIAL DYNAMIC IMPACTS

    SciTech Connect

    Wu, T

    2009-06-25

    Large fuel casks subjected to the combined loads of closure bolt tightening, internal pressure and sequential dynamic impacts present challenges when evaluating their performance in the Hypothetical Accident Conditions (HAC) specified in the Code of Federal Regulations Title 10 Part 71 (10CFR71). Testing is often limited by cost, difficulty in preparing test units and the limited availability of facilities which can carry out such tests. In the past, many casks were evaluated without testing by using simplified analytical methods. In addition, there are no realistic analyses of closure bolt stresses for HAC conditions reported in the open literature. This paper presents a numerical technique for analyzing the accumulated damages of a large fuel cask caused by the sequential loads of the closure bolt tightening and the internal pressure as well as the drop and crash dynamic loads. The bolt preload and the internal pressure are treated as quasi-static loads so that the finite element method with explicit numerical integration scheme based on the theory of wave propagation can be applied. The dynamic impacts with short durations such as the 30-foot drop and the 40-inch puncture for the hypothetical accident conditions specified in 10CFR71 are also analyzed by using the finite-element method with explicit numerical integration scheme.

  16. The importance of replicating genomic analyses to verify phylogenetic signal for recently evolved lineages.

    PubMed

    Fraser, Ceridwen I; McGaughran, Angela; Chuah, Aaron; Waters, Jonathan M

    2016-08-01

    Genomewide SNP data generated by nontargeted methods such as RAD and GBS are increasingly being used in phylogenetic and phylogeographic analyses. When these methods are used in the absence of a reference genome, however, little is known about the locations and evolution of the SNPs. In using such data to address phylogenetic questions, researchers risk drawing false conclusions, particularly if a representative number of SNPs is not obtained. Here, we empirically test the robustness of phylogenetic inference based on SNP data for closely related lineages. We conducted a genomewide analysis of 75 712 SNPs, generated via GBS, of southern bull-kelp (Durvillaea). Durvillaea chathamensis co-occurs with D. antarctica on Chatham Island, but the two species have previously been found to be so genetically similar that the status of the former has been questioned. Our results show that D. chathamensis, which differs from D. antarctica ecologically as well as morphologically, is indeed a reproductively isolated species. Furthermore, our replicated analyses show that D. chathamensis cannot be reliably distinguished phylogenetically from closely related D. antarctica using subsets (ranging in size from 400 to 10 000 sites) of the 40 912 parsimony-informative SNPs in our data set and that bootstrap values alone can give misleading impressions of the strength of phylogenetic inferences. These results highlight the importance of independently replicating SNP analyses to verify that phylogenetic inferences based on nontargeted SNP data are robust. Our study also demonstrates that modern genomic approaches can be used to identify cases of recent or incipient speciation that traditional approaches (e.g. Sanger sequencing of a few loci) may be unable to detect or resolve.

  17. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    PubMed

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.

  18. Analysing the 21 cm signal from the epoch of reionization with artificial neural networks

    NASA Astrophysics Data System (ADS)

    Shimabukuro, Hayato; Semelin, Benoit

    2017-07-01

    The 21 cm signal from the epoch of reionization should be observed within the next decade. While a simple statistical detection is expected with Square Kilometre Array (SKA) pathfinders, the SKA will hopefully produce a full 3D mapping of the signal. To extract from the observed data constraints on the parameters describing the underlying astrophysical processes, inversion methods must be developed. For example, the Markov Chain Monte Carlo method has been successfully applied. Here, we test another possible inversion method: artificial neural networks (ANNs). We produce a training set that consists of 70 individual samples. Each sample is made of the 21 cm power spectrum at different redshifts produced with the 21cmFast code plus the value of three parameters used in the seminumerical simulations that describe astrophysical processes. Using this set, we train the network to minimize the error between the parameter values it produces as an output and the true values. We explore the impact of the architecture of the network on the quality of the training. Then we test the trained network on the new set of 54 test samples with different values of the parameters. We find that the quality of the parameter reconstruction depends on the sensitivity of the power spectrum to the different parameters at a given redshift, that including thermal noise and sample variance decreases the quality of the reconstruction and that using the power spectrum at several redshifts as an input to the ANN improves the quality of the reconstruction. We conclude that ANNs are a viable inversion method whose main strength is that they require a sparse exploration of the parameter space and thus should be usable with full numerical simulations.

  19. Dynamic speckle-interferometer for intracellular processes analyses at high optical magnification

    NASA Astrophysics Data System (ADS)

    Baharev, A. A.; Vladimirov, A. P.; Malygin, A. S.; Mikhailova, Y. A.; Novoselova, I. A.; Yakin, D. I.; Druzhinin, A. V.

    2015-05-01

    At present work dynamic of biospeckles is used for studying processes occurring in cells which arranged in the one layer. The basis of many diseases is changes in the structural and functional properties of the molecular cells components as caused by the influence of external factors and internal functional disorders. Purpose of work is approbation of speckle-interferometer designed for the analysis of cellular metabolism in individual cells. As a parameter, characterizing the metabolic activity of cells used the value of the correlation coefficient (η) of optical signals proportional to the radiation intensity I, recorded at two points in time t. At 320x magnification for the cell diameter of 20 microns value η can be determined in the area size of 6 microns.

  20. Using dynamic population simulations to extend resource selection analyses and prioritize habitats for conservation

    USGS Publications Warehouse

    Heinrichs, Julie; Aldridge, Cameron; O'Donnell, Michael; Schumaker, Nathan

    2017-01-01

    Prioritizing habitats for conservation is a challenging task, particularly for species with fluctuating populations and seasonally dynamic habitat needs. Although the use of resource selection models to identify and prioritize habitat for conservation is increasingly common, their ability to characterize important long-term habitats for dynamic populations are variable. To examine how habitats might be prioritized differently if resource selection was directly and dynamically linked with population fluctuations and movement limitations among seasonal habitats, we constructed a spatially explicit individual-based model for a dramatically fluctuating population requiring temporally varying resources. Using greater sage-grouse (Centrocercus urophasianus) in Wyoming as a case study, we used resource selection function maps to guide seasonal movement and habitat selection, but emergent population dynamics and simulated movement limitations modified long-term habitat occupancy. We compared priority habitats in RSF maps to long-term simulated habitat use. We examined the circumstances under which the explicit consideration of movement limitations, in combination with population fluctuations and trends, are likely to alter predictions of important habitats. In doing so, we assessed the future occupancy of protected areas under alternative population and habitat conditions. Habitat prioritizations based on resource selection models alone predicted high use in isolated parcels of habitat and in areas with low connectivity among seasonal habitats. In contrast, results based on more biologically-informed simulations emphasized central and connected areas near high-density populations, sometimes predicted to be low selection value. Dynamic models of habitat use can provide additional biological realism that can extend, and in some cases, contradict habitat use predictions generated from short-term or static resource selection analyses. The explicit inclusion of population

  1. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.

    PubMed

    Tan, Haiyan; Yang, Kai; Li, Yuxin; Shaw, Timothy I; Wang, Yanyan; Blanco, Daniel Bastardo; Wang, Xusheng; Cho, Ji-Hoon; Wang, Hong; Rankin, Sherri; Guy, Cliff; Peng, Junmin; Chi, Hongbo

    2017-03-21

    The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.

  2. Structural Dynamic Analyses And Test Predictions For Spacecraft Structures With Non-Linearities

    NASA Astrophysics Data System (ADS)

    Vergniaud, Jean-Baptiste; Soula, Laurent; Newerla, Alfred

    2012-07-01

    The overall objective of the mechanical development and verification process is to ensure that the spacecraft structure is able to sustain the mechanical environments encountered during launch. In general the spacecraft structures are a-priori assumed to behave linear, i.e. the responses to a static load or dynamic excitation, respectively, will increase or decrease proportionally to the amplitude of the load or excitation induced. However, past experiences have shown that various non-linearities might exist in spacecraft structures and the consequences of their dynamic effects can significantly affect the development and verification process. Current processes are mainly adapted to linear spacecraft structure behaviour. No clear rules exist for dealing with major structure non-linearities. They are handled outside the process by individual analysis and margin policy, and analyses after tests to justify the CLA coverage. Non-linearities can primarily affect the current spacecraft development and verification process on two aspects. Prediction of flights loads by launcher/satellite coupled loads analyses (CLA): only linear satellite models are delivered for performing CLA and no well-established rules exist how to properly linearize a model when non- linearities are present. The potential impact of the linearization on the results of the CLA has not yet been properly analyzed. There are thus difficulties to assess that CLA results will cover actual flight levels. Management of satellite verification tests: the CLA results generated with a linear satellite FEM are assumed flight representative. If the internal non- linearities are present in the tested satellite then there might be difficulties to determine which input level must be passed to cover satellite internal loads. The non-linear behaviour can also disturb the shaker control, putting the satellite at risk by potentially imposing too high levels. This paper presents the results of a test campaign performed in

  3. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

    PubMed Central

    Martínez-Herrera, Alejandro; Aragón, Jorge; Bermúdez-Cruz, Rosa Ma.; Bazán, Ma. Luisa; Soid-Raggi, Gabriela; Ceja, Víctor; Santos Coy-Arechavaleta, Andrea; Alemán, Víctor; Depardón, Francisco; Montañez, Cecilia

    2015-01-01

    Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy) gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015) 115–120) [1]. PMID:26217814

  4. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-07-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm2. This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress.

  5. Genetic and Structural Analyses of RRNPP Intercellular Peptide Signaling of Gram-Positive Bacteria.

    PubMed

    Neiditch, Matthew B; Capodagli, Glenn C; Prehna, Gerd; Federle, Michael J

    2017-09-06

    Bacteria use diffusible chemical messengers, termed pheromones, to coordinate gene expression and behavior among cells in a community by a process known as quorum sensing. Pheromones of many gram-positive bac, such as Bacillus and Streptococcus, are small, linear peptides secreted from cells and subsequently detected by sensory receptors such as those belonging to the large family ofRRNPP proteins. These proteins are cytoplasmic pheromone receptors sharing a structurally similar pheromone-binding domain that functions allosterically to regulate receptor activity. X-ray crystal structures of prototypical RRNPP members have provided atomic-level insights into their mechanism and regulation by pheromones. This review provides an overview of RRNPP prototype signaling; describes the structure-function of this protein family, which is spread widely among gram-positive bacteria; and suggests approaches to target RRNPP systems in order to manipulate beneficial and harmful bacterial behaviors. Expected final online publication date for the Annual Review of Genetics Volume 51 is November 23, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  6. Next-generation sequencing, phylogenetic signal and comparative mitogenomic analyses in Metacrangonyctidae (Amphipoda: Crustacea).

    PubMed

    Pons, Joan; Bauzà-Ribot, Maria M; Jaume, Damià; Juan, Carlos

    2014-07-06

    Comparative mitochondrial genomic analyses are rare among crustaceans below the family or genus level. The obliged subterranean crustacean amphipods of the family Metacrangonyctidae, found from the Hispaniola (Antilles) to the Middle East, including the Canary Islands and the peri-Mediterranean region, have an evolutionary history and peculiar biogeography that can respond to Tethyan vicariance. Indeed, recent phylogenetic analysis using all protein-coding mitochondrial sequences and one nuclear ribosomal gene have lent support to this hypothesis (Bauzà-Ribot et al. 2012). We present the analyses of mitochondrial genome sequences of 21 metacrangonyctids in the genera Metacrangonyx and Longipodacrangonyx, covering the entire geographical range of the family. Most mitogenomes were attained by next-generation sequencing techniques using long-PCR fragments sequenced by Roche FLX/454 or GS Junior pyro-sequencing, obtaining a coverage depth per nucleotide of up to 281×. All mitogenomes were AT-rich and included the usual 37 genes of the metazoan mitochondrial genome, but showed a unique derived gene order not matched in any other amphipod mitogenome. We compare and discuss features such as strand bias, phylogenetic informativeness, non-synonymous/synonymous substitution rates and other mitogenomic characteristics, including ribosomal and transfer RNAs annotation and structure. Next-generation sequencing of pooled long-PCR amplicons can help to rapidly generate mitogenomic information of a high number of related species to be used in phylogenetic and genomic evolutionary studies. The mitogenomes of the Metacrangonyctidae have the usual characteristics of the metazoan mitogenomes (circular molecules of 15,000-16,000 bp, coding for 13 protein genes, 22 tRNAs and two ribosomal genes) and show a conserved gene order with several rearrangements with respect to the presumed Pancrustacean ground pattern. Strand nucleotide bias appears to be reversed with respect to the

  7. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer

    PubMed Central

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K.; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh’d.; Singh, Ajay P.

    2016-01-01

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p < 0.05) that were assigned to 25 gene networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA-damage and -repair responses, p53 and HIF1α. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID:27354262

  8. Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza

    PubMed Central

    Ge, Qian; Zhang, Yuan; Hua, Wen-Ping; Wu, Yu-Cui; Jin, Xin-Xin; Song, Shuang-Hong; Wang, Zhe-Zhi

    2015-01-01

    Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participate in the JA-mediated accumulation of secondary metabolites, we examined the metabolomic and transcriptomic signatures from Salvia miltiorrhiza. For the metabolome, 35 representative metabolites showing significant changes in rates of accumulation were extracted and identified. We also screened out 2131 differentially expressed unigenes, of which 30 were involeved in the phenolic secondary metabolic pathway, while 25 were in the JA biosynthesis and signal pathways. Among several MeJA-induced novel genes, SmJAZ8 was selected for detailed functional analysis. Transgenic plants over-expressing SmJAZ8 exhibited a JA-insensitive phenotype, suggesting that the gene is a transcriptional regulator in the JA signal pathway of S. miltiorrhiza. Furthermore, this transgenic tool revealed that JAZ genes have novel function in the constitutive accumulation of secondary metabolites. Based on these findings, we propose that the combined strategy of transcriptomic and metabolomic analyses is valuable for efficient discovery of novel genes in plants. PMID:26388160

  9. Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics

    PubMed Central

    Sanborn, Barbara M.

    2007-01-01

    Understanding the basis for the control of myometrial contractant and relaxant signaling pathways is important to understanding how to manage myometrial contractions. Signaling pathways are influenced by the level of expression of the signals and signal pathway components, the location of these components in the appropriate subcellular environment, and covalent modification. Crosstalk between these pathways regulates the effectiveness of signal transduction and represents an important way by which hormones can regulate phenotype. This review deals primarily with signaling pathways that control Ca2+ entry and intracellular release, as well as the interplay between these pathways. PMID:17627855

  10. Stream restoration in dynamic fluvial systems: Scientific approaches, analyses, and tools

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-04-01

    In the United States the average annual investment in river restoration programs is approximately $1 billion. Despite this burgeoning industry, the National Water Quality Inventory, which tracks the health of the nation's rivers, has shown no serious improvement in cumulative river health since the early 1990s. In the AGU monographStream Restoration in Dynamic Fluvial Systems: Scientific Approaches, Analyses, and Tools, editors Andrew Simon, Sean J. Bennett, and Janine M. Castro pull together the latest evidence-based understanding of stream restoration practices, with an aim of guiding the further development of the field and helping to right its apparently unsuccessful course. In this interview, Eos talks to Sean J. Bennett, University of Buffalo, about the culture, practice, and promise of restoring rivers.

  11. A comprehensive tool to analyse dynamic log files from an Elekta-Synergy accelerator

    NASA Astrophysics Data System (ADS)

    Arumugam, Sankar; Xing, Aitang; Pagulayan, Claire; Holloway, Lois

    2014-03-01

    This study presents the development of a software tool 'Treat Check' to analyse the dynamic log files from an Elekta - Synergy accelerator. The software generates formatted output in the form of a plot presenting errors in various treatment delivery parameters such as gantry angle, Multi Leaf Collimator (MLC) leaf position, jaw position and Monitor Units (MU) for each of the control-points (CP) of the treatment beam. The plots are automatically saved in Portable Document Format (pdf). The software also has the functionality to introduce these treatment delivery errors into the original plan in the Pinnacle (Philips) treatment planning system (TPS) in order to assess the clinical impact of treatment delivery errors on delivered dose.

  12. Analyses of heat transfer in stationary and rotating ribbed blade cooling passages using computational fluid dynamics.

    PubMed

    Brewster, R A; Jonnavithula, S

    2001-05-01

    Computational fluid dynamics (CFD) predictions of the flow patterns and heat transfer in simplified ribbed-wall turbine blade cooling passages were performed for representative stationary and rotating conditions. Analyses have been performed with different mesh densities and using different turbulence models to assess the sensitivity of predictions to these variables. Computed local heat transfer results are compared to measurements available in the literature to assess their accuracy. The results generally agree well with experiment, although the peak values of the heat transfer coefficients were under-predicted in the first leg of the channel. Some sensitivity to mesh density was seen, while the choice of near-wall turbulence model appeared to have little effect.

  13. Three isoparametric solid elements for NASTRAN. [for static, dynamic, buckling, and heat transfer analyses

    NASA Technical Reports Server (NTRS)

    Johnson, S. E.; Field, E. I.

    1973-01-01

    Linear, quadratic, and cubic isoparametric hexahedral solid elements have been added to the element library of NASTRAN. These elements are available for static, dynamic, buckling, and heat-transfer analyses. Because the isoparametric element matrices are generated by direct numerical integration over the volume of the element, variations in material properties, temperatures, and stresses within the elements are represented in the computations. In order to compare the accuracy of the new elements, three similar models of a slender cantilever were developed, one for each element. All elements performed well. As expected, however, the linear element model yielded excellent results only when shear behavior predominated. In contrast, the results obtained from the quadratic and cubic element models were excellent in both shear and bending.

  14. Predictability of the monthly North Atlantic Oscillation index based on fractal analyses and dynamic system theory

    NASA Astrophysics Data System (ADS)

    Martínez, M. D.; Lana, X.; Burgueño, A.; Serra, C.

    2010-03-01

    The predictability of the monthly North Atlantic Oscillation, NAO, index is analysed from the point of view of different fractal concepts and dynamic system theory such as lacunarity, rescaled analysis (Hurst exponent) and reconstruction theorem (embedding and correlation dimensions, Kolmogorov entropy and Lyapunov exponents). The main results point out evident signs of randomness and the necessity of stochastic models to represent time evolution of the NAO index. The results also show that the monthly NAO index behaves as a white-noise Gaussian process. The high minimum number of nonlinear equations needed to describe the physical process governing the NAO index fluctuations is evidence of its complexity. A notable predictive instability is indicated by the positive Lyapunov exponents. Besides corroborating the complex time behaviour of the NAO index, present results suggest that random Cantor sets would be an interesting tool to model lacunarity and time evolution of the NAO index.

  15. Using System Dynamic Model and Neural Network Model to Analyse Water Scarcity in Sudan

    NASA Astrophysics Data System (ADS)

    Li, Y.; Tang, C.; Xu, L.; Ye, S.

    2017-07-01

    Many parts of the world are facing the problem of Water Scarcity. Analysing Water Scarcity quantitatively is an important step to solve the problem. Water scarcity in a region is gauged by WSI (water scarcity index), which incorporate water supply and water demand. To get the WSI, Neural Network Model and SDM (System Dynamic Model) that depict how environmental and social factors affect water supply and demand are developed to depict how environmental and social factors affect water supply and demand. The uneven distribution of water resource and water demand across a region leads to an uneven distribution of WSI within this region. To predict WSI for the future, logistic model, Grey Prediction, and statistics are applied in predicting variables. Sudan suffers from severe water scarcity problem with WSI of 1 in 2014, water resource unevenly distributed. According to the result of modified model, after the intervention, Sudan’s water situation will become better.

  16. Nonlinear estimation of coherent phase vibrations for statistical signals through multivariable analyses

    NASA Astrophysics Data System (ADS)

    Deng, Linhua

    2015-07-01

    Three nonlinear analysis techniques, including cross-recurrence plot, line of synchronization, and cross-wavelet transform, are proposed to estimate the coherent phase vibrations of nonlinear and non-stationary time series. The case study utilizes the monthly averages of sunspot areas during the time interval from May 1874 to August 2014. The following prominent results are found: (1) the phase-leading hemisphere of long-term sunspot areas has changed twice in the past 140 years, indicating that the hemispheric imbalances and apparent phase differences on both hemispheres are a prevalent behavior and are not anomalous; (2) the alternating regularity of hemispheric asynchronism exhibits a cyclical pattern of 4.5+3.5 cycles, and the magnetic flux excess in a certain hemisphere during the ascending branch of a cycle can be taken as an indication of the phase-leading hemisphere in this cycle. We firmly believe that powerful nonlinear approaches are more advanced than classical linear methods when they are combined to determine the dynamic complexity of nonlinear physical systems.

  17. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    PubMed Central

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  18. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

  19. Analyses of the dynamic docking test system for advanced mission docking system test programs. [Apollo Soyuz Test Project

    NASA Technical Reports Server (NTRS)

    Gates, R. M.; Williams, J. E.

    1974-01-01

    Results are given of analytical studies performed in support of the design, implementation, checkout and use of NASA's dynamic docking test system (DDTS). Included are analyses of simulator components, a list of detailed operational test procedures, a summary of simulator performance, and an analysis and comparison of docking dynamics and loads obtained by test and analysis.

  20. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism

    PubMed Central

    Pilorge, Marion; Fassier, Coralie; Le Corronc, Hervé; Potey, Anaïs; Bai, Jing; De Gois, Stéphanie; Delaby, Elsa; Assouline, Brigitte; Guinchat, Vincent; Devillard, Françoise; Delorme, Richard; Nygren, Gudrun; Råstam, Maria; Meier, Jochen; Otani, Satoru; Cheval, Hélène; James, Victoria; Topf, Maya; Dear, Neil; Gillberg, Christopher; Leboyer, Marion; Giros, Bruno; Gautron, Sophie; Hazan, Jamilé; Harvey, Robert; Legendre, Pascal; Betancur, Catalina

    2016-01-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2Δex8-9). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2Δex8-9 protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and dramatically reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon branching defects, rescued by injection of wild-type but not GLRA2Δex8-9 or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive impairments

  1. A Dynamic Stimulus-Driven Model of Signal Detection

    ERIC Educational Resources Information Center

    Turner, Brandon M.; Van Zandt, Trisha; Brown, Scott

    2011-01-01

    Signal detection theory forms the core of many current models of cognition, including memory, choice, and categorization. However, the classic signal detection model presumes the a priori existence of fixed stimulus representations--usually Gaussian distributions--even when the observer has no experience with the task. Furthermore, the classic…

  2. A Dynamic Stimulus-Driven Model of Signal Detection

    ERIC Educational Resources Information Center

    Turner, Brandon M.; Van Zandt, Trisha; Brown, Scott

    2011-01-01

    Signal detection theory forms the core of many current models of cognition, including memory, choice, and categorization. However, the classic signal detection model presumes the a priori existence of fixed stimulus representations--usually Gaussian distributions--even when the observer has no experience with the task. Furthermore, the classic…

  3. Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort

    PubMed Central

    McAuley, Emily M.

    2016-01-01

    The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies. PMID:27936045

  4. Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort.

    PubMed

    McAuley, Emily M; Bertram, Susan M

    2016-01-01

    The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies.

  5. Parameter space exploration within dynamic simulations of signaling networks.

    PubMed

    De Ambrosi, Cristina; Barla, Annalisa; Tortolina, Lorenzo; Castagnino, Nicoletta; Pesenti, Raffaele; Verri, Alessandro; Ballestrero, Alberto; Patrone, Franco; Parodi, Silvio

    2013-02-01

    We started offering an introduction to very basic aspects of molecular biology, for the reader coming from computer sciences, information technology, mathematics. Similarly we offered a minimum of information about pathways and networks in graph theory, for a reader coming from the bio-medical sector. At the crossover about the two different types of expertise, we offered some definition about Systems Biology. The core of the article deals with a Molecular Interaction Map (MIM), a network of biochemical interactions involved in a small signaling-network sub-region relevant in breast cancer. We explored robustness/sensitivity to random perturbations. It turns out that our MIM is a non-isomorphic directed graph. For non physiological directions of propagation of the signal the network is quite resistant to perturbations. The opposite happens for biologically significant directions of signal propagation. In these cases we can have no signal attenuation, and even signal amplification. Signal propagation along a given pathway is highly unidirectional, with the exception of signal-feedbacks, that again have a specific biological role and significance. In conclusion, even a relatively small network like our present MIM reveals the preponderance of specific biological functions over unspecific isomorphic behaviors. This is perhaps the consequence of hundreds of millions of years of biological evolution.

  6. Dynamics of BMP signaling in limb bud mesenchyme and polydactyly.

    PubMed

    Norrie, Jacqueline L; Lewandowski, Jordan P; Bouldin, Cortney M; Amarnath, Smita; Li, Qiang; Vokes, Martha S; Ehrlich, Lauren I R; Harfe, Brian D; Vokes, Steven A

    2014-09-15

    Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis.

  7. Dynamic coordination of innate immune signaling and Insulin signaling regulates systemic responses to localized DNA damage

    PubMed Central

    Karpac, Jason; Younger, Andrew; Jasper, Heinrich

    2011-01-01

    Metazoans adapt to changing environmental conditions and to harmful challenges by attenuating growth and metabolic activities systemically. Recent studies in mice and flies indicate that endocrine signaling interactions between Insulin/IGF signaling (IIS) and innate immune signaling pathways are critical for this adaptation, yet the temporal and spatial hierarchy of these signaling events remains elusive. Here we identify and characterize a program of signaling interactions that regulates the systemic response of the Drosophila larva to localized DNA damage. We provide evidence that epidermal DNA damage induces an innate immune response that is kept in check by systemic repression of IIS activity. IIS repression induces NFkB/Relish signaling in the fatbody, which is required for recovery of IIS activity in a second phase of the systemic response to DNA damage. This systemic response to localized DNA damage thus coordinates growth and metabolic activities across tissues, ensuring growth homeostasis and survival of the animal. PMID:21664581

  8. A system of recurrent neural networks for modularising, parameterising and dynamic analysis of cell signalling networks.

    PubMed

    Samarasinghe, S; Ling, H

    2017-02-04

    In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model. Trained sub-models are assembled into a whole system RNN which is then subjected to systems dynamics and sensitivity analyses. The concept is illustrated by application to G1/S transition in cell cycle using Iwamoto et al. (2008) ODE model. We decomposed the G1/S network into 3 sub-models: (i) E2F transcription factor release; (ii) E2F and CycE positive feedback loop for elevating cyclin levels; and (iii) E2F and CycA negative feedback to degrade E2F. The trained sub-models accurately represented system dynamics and parameters were in good agreement with the ODE model. The whole system RNN however revealed couple of parameters contributing to compounding errors due to feedback and required refinement to sub-model 2. These related to the reversible reaction between CycE/CDK2 and p27, its inhibitor. The revised whole system RNN model very accurately matched dynamics of the ODE system. Local sensitivity analysis of the whole system model further revealed the most dominant influence of the above two parameters in perturbing G1/S transition, giving support to a recent hypothesis that the release of inhibitor p27 from Cyc/CDK complex triggers cell cycle stage transition. To make the model useful in a practical setting, we modified each RNN sub-model with a time relay switch to facilitate larger interval input data (≈20min) (original model used data for 30s or less) and retrained them that produced

  9. Insights into soil carbon dynamics across climatic gradients from carbon-pool specific radiocarbon analyses

    NASA Astrophysics Data System (ADS)

    van der Voort, Tessa Sophia; Hagedorn, Frank; McIntyre, Cameron; Zell, Claudia; Eglinton, Timothy Ian

    2017-04-01

    Soil carbon constitutes the largest terrestrial reservoir of organic carbon, and therefore understanding the mechanisms and drivers of carbon stabilization is crucial, especially in the framework of climate change. The understanding of the dependence of soil organic turnover in specific carbon pools as related to e.g. climate, soil texture and mineralogy is limited. In this framework, radiocarbon constitutes a uniquely powerful tool that help to unravel carbon dynamics from decadal to millennial timescales. This project combines bulk and pool-specific radiocarbon analyses in the top and deep soil on a wide range of forested soils that span a large climatic gradient (MAT 1.3-9.2°C, MAP 600 to 2100 mm m-2y-1). These well-studies sites are part of the Long-Term Forest Ecosystem Research (LWF) program of the Swiss Federal Institute for Forest, Snow and Landscape research (WSL). This study aims to combine the insights gained from bulk and pool-specific turnover to environmental conditions and molecular composition of soil carbon. The pools investigated span the mineral-associated (occluded and heavy fractions from density fractionation) and potentially water-soluble (free light fractions from density fractionation and water extractable organic carbon) organic carbon fractions. Pool-specific radiocarbon work is augmented by the measurement of abundance of compounds such as alkanes, fatty acids and lignin phenols on a subset of samples. Initial results show disparate patterns depending on soil type and in particular soil texture, which could be indicative of various stabilization mechanisms in different soils. Overall, this study provides new insights into the controls of soil organic matter dynamics as related to environmental conditions, in particular in specific sub-pools of carbon.

  10. Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability

    PubMed Central

    Rubel, Tymon; Paziewska, Agnieszka; Mikula, Michal; Jarosz, Dorota; Pachlewski, Jacek; Oledzki, Janusz; Ostrowsk, Jerzy

    2010-01-01

    Background Clinical progression of colorectal cancers (CRC) may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings Studies were performed on normal mucosa, adenoma, and carcinoma samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data was generated using two normalization algorithms: MAS5.0 and GCRMA with least-variant set (LVS). The data was evaluated using pair-wise comparisons and data decomposition into singular value decomposition (SVD) modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Expressional profiles obtained in 105 samples of whole tissue sections were used to establish oncogenic signaling alterations in progression of CRC, while those representing 40 microdissected specimens were used to select differences in KEGG pathways between epithelium and mucosa. Based on a consensus of the results obtained by two normalization algorithms, and two probe set sorting criteria, we identified 14 and 17 KEGG signaling and metabolic pathways that are significantly altered between normal and tumor samples and between benign and malignant tumors, respectively. Several of them were also selected from the raw microarray data of 2 recently published studies (GSE4183 and GSE8671). Conclusion/Significance Although the proposed strategy is computationally complex and labor–intensive, it may reduce the number of false results. PMID:20957034

  11. Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation.

    PubMed

    Murase, Tomokazu; Umeda, Masahiro; Fukunaga, Masaki; Tanaka, Chuzo; Higuchi, Toshihiro

    2013-01-01

    We used deconvolution analysis to examine temporal changes in brain activity after acupuncture stimulation and assess brain responses without expected reference functions. We also examined temporal changes in brain activity after sham acupuncture (noninsertive) and scrubbing stimulation. We divided 26 healthy right-handed adults into a group of 13 who received real acupuncture with manual manipulation and a group of 13 who received both tactical stimulations. Functional magnetic resonance imaging (fMRI) sequences consisted of four 15-s stimulation blocks (ON) interspersed between one 30-s and four 45-s rest blocks (OFF) for a total scanning time of 270 s. We analyzed data by using Statistical Parametric Mapping 8 (SPM8), MarsBaR, and Analysis of Functional NeuroImages (AFNI) software. For statistical analysis, we used 3dDeconvolve, part of the AFNI package, to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis, and we tested the time courses of the extracted IRFs for the stimulations. We found stimulus-specific impulse responses of blood oxygen level-dependent (BOLD) signals in various brain regions. We observed significantly delayed and long-sustained increases of BOLD signals in several brain regions following real acupuncture compared to sham acupuncture and palm scrubbing, which we attribute to peripheral nocireceptors, flare responses, and processing of the central nervous system. Acupuncture stimulation induced continued activity that was stronger than activity after the other stimulations. We used tent function deconvolution to process fMRI data for acupuncture stimulation and found delayed increasing and delayed decreasing changes in BOLD signal in the somatosensory areas and areas related to pain perception. Deconvolution analyses with tent functions are expected to be useful in extracting complicated and associated brain activity that is delayed and sustained for a long period after various stimulations.

  12. Multi-Platform Metabolomic Analyses of Ergosterol-Induced Dynamic Changes in Nicotiana tabacum Cells

    PubMed Central

    Tugizimana, Fidele; Steenkamp, Paul A.; Piater, Lizelle A.; Dubery, Ian A.

    2014-01-01

    Metabolomics is providing new dimensions into understanding the intracellular adaptive responses in plants to external stimuli. In this study, a multi-technology-metabolomic approach was used to investigate the effect of the fungal sterol, ergosterol, on the metabolome of cultured tobacco cells. Cell suspensions were treated with different concentrations (0–1000 nM) of ergosterol and incubated for different time periods (0–24 h). Intracellular metabolites were extracted with two methods: a selective dispersive liquid-liquid micro-extraction and a general methanol extraction. Chromatographic techniques (GC-FID, GC-MS, GC×GC-TOF-MS, UHPLC-MS) and 1H NMR spectroscopy were used for quantitative and qualitative analyses. Multivariate data analyses (PCA and OPLS-DA models) were used to extract interpretable information from the multidimensional data generated from the analytical techniques. The results showed that ergosterol triggered differential changes in the metabolome of the cells, leading to variation in the biosynthesis of secondary metabolites. PCA scores plots revealed dose- and time-dependent metabolic variations, with optimal treatment conditions being found to be 300 nM ergosterol and an 18 h incubation period. The observed ergosterol-induced metabolic changes were correlated with changes in defence-related metabolites. The ‘defensome’ involved increases in terpenoid metabolites with five antimicrobial compounds (the bicyclic sesquiterpenoid phytoalexins: phytuberin, solavetivone, capsidiol, lubimin and rishitin) and other metabolites (abscisic acid and phytosterols) putatively identified. In addition, various phenylpropanoid precursors, cinnamic acid derivatives and - conjugates, coumarins and lignin monomers were annotated. These annotated metabolites revealed a dynamic reprogramming of metabolic networks that are functionally correlated, with a high complexity in their regulation. PMID:24498209

  13. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    PubMed

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  14. Molecular dynamics and QM/MM-based 3D interaction analyses of cyclin-E inhibitors.

    PubMed

    Pasha, Farhan Ahmad; Neaz, Mohammad Morshed

    2013-02-01

    Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently undergoing clinical trials, but possibilities remain for the identification and development of novel and improved inhibitors. For example, in silico targeting of ATP-competitive inhibitors of CDKs is of special interest. A series of 3,5-diaminoindazoles was studied using molecular docking and comparative field analyses. We used post-docking short time molecular dynamics (MD) simulation to account for receptor flexibility. The three types of structures, i.e., the highest energy, lowest energy and the structure most resembling the X-ray structure (three complexes) were identified for all ligands. QM/MM energy calculations were performed using a DFT b3lyp/6-31 g* and MM OPLS-2005 force field. Conceptual DFT properties such as the interaction energy of ligand to protein, global hardness (η), HOMO density, electrostatic potential, and electron density were calculated and related to inhibitory activity. CoMFA and CoMSIA were used to account for steric and electrostatic interactions. The results of this study provide insight into the bioactive conformation, interactions involved, and the effect of different drug fragments over different biological activities.

  15. Analysing the temporal water quality dynamics of Lake Basaka, Central Rift Valley of Ethiopia

    NASA Astrophysics Data System (ADS)

    Olumana Dinka, Megersa

    2017-01-01

    This study presents the general water quality status and temporal quality dynamics of Lake Basaka water in the past about 5 decades. Water samples were collected and analysed for important physico-chemical quality parameters following standard procedures. The result showed that Lake Basaka water is highly saline and alkaline and experiencing a general reducing trends in ionic concentrations of quality parameters due to the dilution effect. About 10-fold reduction of total ionic concentration occurred in the Lake over the period of 2 decades (1960-1980). There was a sharp and fast decline in EC, Cl, SO4, Na, and K ions from early 1960s up to the late 1980s, and then became relatively stable. Some ions (eg. Na, Ca, Mg, Cl, SO4) are showing increment in recent years. This characteristics of the lake water is terrible in relation to its potential to inundate the nearby areas in the near future. The expansion of such quality water has negative effects on the water resources of the region, especially soil quality, drainage and groundwater, in terms of salinity, sodicity and specific ion toxicity. The regimes of soil moisture, solute and groundwater could be affected, concurrently affecting the productivity and sustainability of the sugar estate. Thus, there is an urgent need to identify the potential sources of water and chemicals to the lake and devise an appropriate mitigation and/or remedial measures.

  16. A dynamic interface between ubiquitylation and cAMP signaling.

    PubMed

    Rinaldi, Laura; Sepe, Maria; Donne, Rossella Delle; Feliciello, Antonio

    2015-01-01

    Phosphorylation waves drive the propagation of signals generated in response to hormones and growth factors in target cells. cAMP is an ancient second messenger implicated in key biological functions. In mammals, most of the effects elicited by cAMP are mediated by protein kinase A (PKA). Activation of the kinase by cAMP results in the phosphorylation of a variety of cellular substrates, leading to differentiation, proliferation, survival, metabolism. The identification of scaffold proteins, namely A-Kinase Anchor proteins (AKAPs), that localize PKA in specific cellular districts, provided critical cues for our understanding of the role played by cAMP in cell biology. Multivalent complexes are assembled by AKAPs and include signaling enzymes, mRNAs, adapter molecules, receptors and ion channels. A novel development derived from the molecular analysis of these complexes nucleated by AKAPs is represented by the presence of components of the ubiquitin-proteasome system (UPS). More to it, the AKAP complex can be regulated by the UPS, eliciting relevant effects on downstream cAMP signals. This represents a novel, yet previously unpredicted interface between compartmentalized signaling and the UPS. We anticipate that impairment of these regulatory mechanisms could promote cell dysfunction and disease. Here, we will focus on the reciprocal regulation between cAMP signaling and UPS, and its relevance to human degenerative and proliferative disorders.

  17. Signal-dependent dynamics of transcription factor translocation controls gene expression

    PubMed Central

    Hao, Nan; O'Shea, Erin K.

    2014-01-01

    Summary Information about environmental stimuli is often transmitted using common signalling molecules, but the mechanisms that ensure signalling specificity are not entirely known. Here we show that the identities and intensities of different stresses are transmitted by modulation of the amplitude, duration or frequency of nuclear translocation of the budding yeast general stress responsive transcription factor Msn2. Through artificial control of the dynamics of Msn2 translocation, we reveal how distinct dynamical schemes differentially affect reporter gene expression. Using a simple model, we predict stress-induced reporter gene expression from single-cell translocation dynamics. We then demonstrate that the response of natural target genes to dynamical modulation of Msn2 translocation is influenced by differences in the kinetics of promoter transitions and transcription factor binding properties. Thus, multiple environmental signals can trigger qualitatively different dynamics of a single transcription factor, and influence gene expression patterns. PMID:22179789

  18. Dopamine D1 signaling organizes network dynamics underlying working memory.

    PubMed

    Roffman, Joshua L; Tanner, Alexandra S; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J; Ho, New Fei; Nitenson, Adam Z; Chonde, Daniel B; Greve, Douglas N; Abi-Dargham, Anissa; Buckner, Randy L; Manoach, Dara S; Rosen, Bruce R; Hooker, Jacob M; Catana, Ciprian

    2016-06-01

    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.

  19. Dopamine D1 signaling organizes network dynamics underlying working memory

    PubMed Central

    Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas N.; Abi-Dargham, Anissa; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian

    2016-01-01

    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID:27386561

  20. Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway

    SciTech Connect

    Shankaran, Harish; Wiley, H. S.

    2010-12-01

    The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15-30 minutes. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of 1-2h. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.

  1. Dynamic Hedgehog signalling pathway activity in germline stem cells.

    PubMed

    Sahin, Z; Szczepny, A; McLaughlin, E A; Meistrich, M L; Zhou, W; Ustunel, I; Loveland, K L

    2014-03-01

    Although the contribution of Hedgehog (Hh) signalling to stem cell development and oncogenesis is well recognised, its importance for spermatogonial stem cells (SSCs) has not been established. Here we interrogate adult rat SSCs using an established model in which only undifferentiated spermatogonial cells remain in the testis at 15 weeks following irradiation, and spermatogonial differentiation is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH-ant) administration. Synthesis of Hh pathway components in untreated adult rat testes was compared with that in irradiated testes prior to and after GnRH-ant exposure using in situ hybridization. In adult testes with complete spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization. Spermatogenic cells were identified as sites of Hh signalling through detection of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the key downstream target of Hh signalling, Gli1 and the Hh transcriptional activator, Gli2. Remarkably, the undifferentiated spermatogonia present in irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2, revealing the potential for an autocrine Hh signalling loop to sustain undifferentiated spermatogonial cells. These transcripts became undetectable by in situ hybridization following GnRH-ant induction of spermatogonial differentiation, however, detection of Gli1 protein in spermatogonia in all groups indicates that Hh signalling is sustained. This is the first evidence of active Hh signalling in mammalian male germline stem cells, as has been documented for some cancer stem cells.

  2. Sparse approximation of long-term biomedical signals for classification via dynamic PCA.

    PubMed

    Xie, Shengkun; Jin, Feng; Krishnan, Sridhar

    2011-01-01

    Sparse approximation is a novel technique in applications of event detection problems to long-term complex biomedical signals. It involves simplifying the extent of resources required to describe a large set of data sufficiently for classification. In this paper, we propose a multivariate statistical approach using dynamic principal component analysis along with the non-overlapping moving window technique to extract feature information from univariate long-term observational signals. Within the dynamic PCA framework, a few principal components plus the energy measure of signals in principal component subspace are highly promising for applying event detection problems to both stationary and non-stationary signals. The proposed method has been first tested using synthetic databases which contain various representative signals. The effectiveness of the method is then verified with real EEG signals for the purpose of epilepsy diagnosis and epileptic seizure detection. This sparse method produces a 100% classification accuracy for both synthetic data and real single channel EEG data.

  3. Ligand-binding dynamics rewire cellular signaling via Estrogen Receptor-α

    PubMed Central

    Srinivasan, Sathish; Nwachukwu, Jerome C.; Parent, Alex A.; Cavett, Valerie; Nowak, Jason; Hughes, Travis S.; Kojetin, Douglas J.; Katzenellenbogen, John A.; Nettles, Kendall W.

    2013-01-01

    Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. Here, we compare a set of ER ligands having dynamic binding orientation (dynamic ligands) with a control set of isomers that are constrained to bind in a single orientation (constrained ligands). Proliferation of breast cancer cells directed by constrained ligands is associated with DNA binding, coactivator recruitment and activation of the estrogen-induced gene GREB1, reflecting a highly interconnected signaling network. In contrast, proliferation driven by dynamic ligands is associated with induction of ERα-mediated transcription in a DNA-binding domain (DBD)-dependent manner. Further, dynamic ligands displayed enhanced anti-inflammatory activity. The DBD-dependent profile was predictive of these signaling patterns in a larger diverse set of natural and synthetic ligands. Thus, ligand dynamics directs unique signaling pathways, and reveals a novel role of the DBD in allosteric control of ERα-mediated signaling. PMID:23524984

  4. Beyond static biomarkers--The dynamic response potential of signaling networks as an alternate biomarker?

    PubMed

    Kim, Jaeyeon; Schoeberl, Birgit

    2015-12-22

    In this week's issue of Science Signaling, Fey et al. introduce a new type of biomarker. Using the example of neuroblastoma, the authors demonstrate that patient-specific differences in the computed property (the Hill coefficient) of the dynamics of a pathway involved in cell death signaling outperformed the prognostic capability of any single static biomarker alone or in combination.

  5. Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling

    PubMed Central

    Burroughs, A. Maxwell; Zhang, Dapeng; Schäffer, Daniel E.; Iyer, Lakshminarayan M.; Aravind, L.

    2015-01-01

    Cyclic di- and linear oligo-nucleotide signals activate defenses against invasive nucleic acids in animal immunity; however, their evolutionary antecedents are poorly understood. Using comparative genomics, sequence and structure analysis, we uncovered a vast network of systems defined by conserved prokaryotic gene-neighborhoods, which encode enzymes generating such nucleotides or alternatively processing them to yield potential signaling molecules. The nucleotide-generating enzymes include several clades of the DNA-polymerase β-like superfamily (including Vibrio cholerae DncV), a minimal version of the CRISPR polymerase and DisA-like cyclic-di-AMP synthetases. Nucleotide-binding/processing domains include TIR domains and members of a superfamily prototyped by Smf/DprA proteins and base (cytokinin)-releasing LOG enzymes. They are combined in conserved gene-neighborhoods with genes for a plethora of protein superfamilies, which we predict to function as nucleotide-sensors and effectors targeting nucleic acids, proteins or membranes (pore-forming agents). These systems are sometimes combined with other biological conflict-systems such as restriction-modification and CRISPR/Cas. Interestingly, several are coupled in mutually exclusive neighborhoods with either a prokaryotic ubiquitin-system or a HORMA domain-PCH2-like AAA+ ATPase dyad. The latter are potential precursors of equivalent proteins in eukaryotic chromosome dynamics. Further, components from these nucleotide-centric systems have been utilized in several other systems including a novel diversity-generating system with a reverse transcriptase. We also found the Smf/DprA/LOG domain from these systems to be recruited as a predicted nucleotide-binding domain in eukaryotic TRPM channels. These findings point to evolutionary and mechanistic links, which bring together CRISPR/Cas, animal interferon-induced immunity, and several other systems that combine nucleic-acid-sensing and nucleotide-dependent signaling

  6. Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

    PubMed Central

    Zaade, Daniela; Schmitz, Jennifer; Benke, Eileen; Klare, Sabrina; Seidel, Kerstin; Kirsch, Sebastian; Goldin-Lang, Petra; Zollmann, Frank S.; Unger, Thomas; Funke-Kaiser, Heiko

    2013-01-01

    The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis. PMID:23469216

  7. Analyses of the soil surface dynamic of South African Kalahari salt pans based on hyperspectral and multitemporal data

    NASA Astrophysics Data System (ADS)

    Milewski, Robert; Chabrillat, Sabine; Behling, Robert; Mielke, Christian; Schleicher, Anja Maria; Guanter, Luis

    2016-04-01

    The consequences of climate change represent a major threat to sustainable development and growth in Southern Africa. Understanding the impact on the geo- and biosphere is therefore of great importance in this particular region. In this context the Kalahari salt pans (also known as playas or sabkhas) and their peripheral saline and alkaline habitats are an ecosystem of major interest. They are very sensitive to environmental conditions, and as thus hydrological, mineralogical and ecological responses to climatic variations can be analysed. Up to now the soil composition of salt pans in this area have been only assessed mono-temporally and on a coarse regional scale. Furthermore, the dynamic of the salt pans, especially the formation of evaporites, is still uncertain and poorly understood. High spectral resolution remote sensing can estimate evaporite content and mineralogy of soils based on the analyses of the surface reflectance properties within the Visible-Near InfraRed (VNIR 400-1000 nm) and Short-Wave InfraRed (SWIR 1000-2500 nm) regions. In these wavelength regions major chemical components of the soil interact with the electromagnetic radiation and produce characteristic absorption features that can be used to derive the properties of interest. Although such techniques are well established for the laboratory and field scale, the potential of current (Hyperion) and upcoming spaceborne sensors such as EnMAP for quantitative mineralogical and salt spectral mapping is still to be demonstrated. Combined with hyperspectral methods, multitemporal remote sensing techniques allow us to derive the recent dynamic of these salt pans and link the mineralogical analysis of the pan surface to major physical processes in these dryland environments. In this study we focus on the analyses of the Namibian Omongwa salt pans based on satellite hyperspectral imagery and multispectral time-series data. First, a change detection analysis is applied using the Iterative

  8. Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

    PubMed Central

    Čokić, Vladan P.; Mossuz, Pascal; Han, Jing; Socoro, Nuria; Beleslin-Čokić, Bojana B.; Mitrović, Olivera; Subotički, Tijana; Diklić, Miloš; Leković, Danijela; Gotić, Mirjana; Puri, Raj K.; Noguchi, Constance Tom; Schechter, Alan N.

    2015-01-01

    The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34+ cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34+ cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34+ cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34+ cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34+ cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34+ cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling. PMID:26275051

  9. Nonlinear Spatial-Temporal Spectral Analyses for Diagnosing Solar 11-Year Signal in the Northern Hemisphere Atmosphere

    NASA Astrophysics Data System (ADS)

    Powell, A. M.; Chen, M.

    2005-12-01

    The major dilemma in the search for a Sun-Earth connection is tiny solar output variations appear insignificant relative to dynamic atmospheric changes while many synoptic and climatic parameters are found to be significantly correlated with the solar variation at different time scales. Based on previous analysis, the solar variations are assumed to exert their influence through nonlinear modulation of the existing dynamic or thermodynamic processes. Nonlinear spatial-temporal spectral analysis is helpful for identifying nonlinear solar signals in the atmospheric observations and establishing nonlinear feedback mechanisms. Using the 50-year NCEP/NCAR reanalysis data, an extensive spatial-temp spectral analysis is performed. Fourier transformation is first applied latitude by latitude to get zonal waves of different spatial scales. The time series of the amplitude (energy) of each wave is filtered to isolate different time-scale waves. From the viewpoint of linear wave theory, these waves are assumed to carry atmospheric energy derived from the original sources and the atmospheric response to the source functions. The temporal change of wave amplitude is closely related to the source energy change, such as boundary condition change, or nonlinear adjustment of background state (energy exchange from different scales), etc. The relevant spatial-temp spectral structure change associated with solar variations will be addressed in this study. The results suggest nonlinear atmospheric processes may couple solar variation with atmospheric variations.

  10. Signal quality of the LHC AC dipoles and its impact on beam dynamics

    SciTech Connect

    Miyamoto, R.; Cattin, M.; Serrano, J.; Tomas, R.

    2010-05-23

    The adiabaticity of the AC dipole might be compromised by noise or unwanted frequency components in its signal. An effort has been put to characterize and optimize the signal quality of the LHC AC dipoles. The measured signal is used in realistic simulations in order to evaluate its impact on beam dynamics and to ultimately establish safe margins for the operation of the LHC AC dipoles.

  11. Spectral signals from electronic dynamics in sodium clusters

    SciTech Connect

    Calvayrac, F.; Reinhard, P.G.; Suraud, E.

    1997-03-01

    We study the dynamics of the electron cloud in sodium clusters for small and large amplitude excitations in the time-dependent local-density approximation (TDLDA), without referring to linear approximations. In particular, we discuss the interpretation of strength function and power spectrum as obtained from dynamical calculations. We demonstrate the constructive and destructive interference contained in the various spectral states. We search for a special signature of nonlinear couplings in the large amplitude regime, but do not find pronounced effects. {copyright} 1997 Academic Press, Inc.

  12. Comparative proteome analyses reveal that nitric oxide is an important signal molecule in the response of rice to aluminum toxicity.

    PubMed

    Yang, Liming; Tian, Dagang; Todd, Christopher D; Luo, Yuming; Hu, Xiangyang

    2013-03-01

    Acidic soils inhibit crop yield and reduce grain quality. One of the major contributing factors to acidic soil is the presence of soluble aluminum (Al(3+)) ions, but the mechanisms underlying plant responses to Al(3+) toxicity remain elusive. Nitric oxide (NO) is an important messenger and participates in various plant physiological responses. Here, we demonstrate that Al(3+) induced an increase of NO in rice seedlings; adding exogenous NO alleviated the Al(3+) toxicity related to rice growth and photosynthetic capacity, effects that could be reversed by suppressing NO metabolism. Comparative proteomic analyses successfully identified 92 proteins that showed differential expression after Al(3+) or NO treatment. In particular, some of the proteins are involved in reactive oxygen species (ROS) and reactive nitrogen species (RNS) metabolism. Further analyses confirmed that NO treatment reduced Al(3+)-induced ROS and RNS toxicities by increasing the activities and protein expression of antioxidant enzymes, as well as S-nitrosoglutathione reductase (GSNOR). Suppressing GSNOR enzymatic activity aggravated Al(3+) damage to rice and increased the accumulation of RNS. NO treatment altered the expression of proteins associated with cell wall synthesis, cell division and cell structure, calcium signaling and defense responses. On the basis of these results, we propose that NO activates multiple pathways that enhance rice adaptation to Al(3+) toxicity. Such findings may be applicable to crop engineering to enhance yield and improve stress tolerance.

  13. Who Is Overeducated and Why? Probit and Dynamic Mixed Multinomial Logit Analyses of Vertical Mismatch in East and West Germany

    ERIC Educational Resources Information Center

    Boll, Christina; Leppin, Julian Sebastian; Schömann, Klaus

    2016-01-01

    Overeducation potentially signals a productivity loss. With Socio-Economic Panel data from 1984 to 2011 we identify drivers of educational mismatch for East and West medium and highly educated Germans. Addressing measurement error, state dependence and unobserved heterogeneity, we run dynamic mixed multinomial logit models for three different…

  14. Who Is Overeducated and Why? Probit and Dynamic Mixed Multinomial Logit Analyses of Vertical Mismatch in East and West Germany

    ERIC Educational Resources Information Center

    Boll, Christina; Leppin, Julian Sebastian; Schömann, Klaus

    2016-01-01

    Overeducation potentially signals a productivity loss. With Socio-Economic Panel data from 1984 to 2011 we identify drivers of educational mismatch for East and West medium and highly educated Germans. Addressing measurement error, state dependence and unobserved heterogeneity, we run dynamic mixed multinomial logit models for three different…

  15. Integration of Predictive Routing Information with Dynamic Traffic Signal Control

    DTIC Science & Technology

    1994-05-01

    vehicles without the on-board guidance aid (Harris, S., Rabone , A., et.al., 1992). The simulation developed was called ROute GUidance Simulation (ROGUS...Florida. Harris, S., Rabone , A., et.al. 1992. ROGUS: A Simulation of Dynamic Route Guidance Systems. Traffic Engineering and Control(33)327-329

  16. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    PubMed Central

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  17. Near-tropopause structure and dynamics from comparisons of total column ozone and model analyses

    NASA Astrophysics Data System (ADS)

    Olsen, Mark Allan

    This study makes comparisons between observed total column ozone (or simply total ozone) from the Earth Probe Total Ozone Mapping Spectrometer (EP/TOMS) and mesoscale model analyses fields for midlatitude, baroclinic cyclone cases. We emphasize the consistency and agreement of total ozone fields with meteorological quantities at smaller scales than previously demonstrated. The results may aid in assimilation of total ozone into models to improve dynamics and forecasting ability. Significant to stratosphere-troposphere exchange studies, the use of total ozone data to identify potential regions of cross- tropopause transport is also illustrated. In case studies of large-scale, midlatitude cyclones over the United States, fine-scale consistency is shown for total ozone and the Mesoscale Analysis and Prediction System (MAPS) model analysis fields. The tropopause pressure field shows good agreement with total ozone outside of regions of stratosphere-troposphere exchange (STE). Geopotential height contours on isobaric surfaces near the tropopause are seen to compare well to total ozone. Complex vertical structure of potential vorticity (PV) in the lower stratosphere can be associated with small scale total ozone maxima and minima. In addition, EP/TOMS retrieval errors on the order of ~10% are identified with high thunderstorm cloud anvils, particularly along frontal zones. Two types of STE are discussed in relation to the evidence and their signature within the model and total ozone fields. ``PV-holes'' of varying strengths are frequently found near the center or eastern part of cyclones. These appear as isolated regions of tropospheric PV values and enhanced total ozone. Back trajectories illustrate that the destruction of PV by precipitation-induced latent heating causes a raising of the PV-defined tropopause, leaving stratospheric air below. In the second type of STE, cross-jet exchange along the southern edge of the cyclone, total ozone is not observed to be

  18. Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses

    NASA Astrophysics Data System (ADS)

    Kaiser, K.; Benner, R. H.

    2013-12-01

    Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

  19. The impacts of hypnotic susceptibility on chaotic dynamics of EEG signals during standard tasks of Waterloo-Stanford Group Scale.

    PubMed

    Yargholi, Elahe'; Nasrabadi, Ali Motie

    2013-05-01

    Chaotic features of hypnotic EEG (electroencephalograph), recorded during standard tasks of Waterloo-Stanford Group Scale of hypnotic susceptibility (WSGS), were used to investigate the underlying dynamic of tasks and analyse the effect of hypnotic depth and concentration on EEG signals. Results demonstrate: (1) More efficiency of Higuchi dimension in comparison with Correlation dimension to distinguish subjects from different hypnotizable groups, (2) Channels with significantly different chaotic features among people from various hypnotizability levels in tasks, (3) High level of consistency among discriminating channels of tasks with function of brain's lobes, (4) Most affectability of medium hypnotizable subjects and (5) Rise in fractal dimensions due to increase in hypnosis depth.

  20. Nonlinear dynamics of the voice: Signal analysis and biomechanical modeling

    NASA Astrophysics Data System (ADS)

    Herzel, Hanspeter; Berry, David; Titze, Ingo; Steinecke, Ina

    1995-03-01

    Irregularities in voiced speech are often observed as a consequence of vocal fold lesions, paralyses, and other pathological conditions. Many of these instabilities are related to the intrinsic nonlinearities in the vibrations of the vocal folds. In this paper, bifurcations in voice signals are analyzed using narrow-band spectrograms. We study sustained phonation of patients with laryngeal paralysis and data from an excised larynx experiment. These spectrograms are compared with computer simulations of an asymmetric 2-mass model of the vocal folds.

  1. Dynamics of long-distance signaling via plant vascular tissues

    PubMed Central

    Notaguchi, Michitaka; Okamoto, Satoru

    2015-01-01

    Plant vascular systems are constructed by specific cell wall modifications through which cells are highly specialized to make conduits for water and nutrients. Xylem vessels are formed by thickened cell walls that remain after programmed cell death, and serve as water conduits from the root to the shoot. In contrast, phloem tissues consist of a complex of living cells, including sieve tube elements and their neighboring companion cells, and translocate photosynthetic assimilates from mature leaves to developing young tissues. Intensive studies on the content of vascular flow fluids have unveiled that plant vascular tissues transport various types of gene product, and the transport of some provides the molecular basis for the long-distance communications. Analysis of xylem sap has demonstrated the presence of proteins in the xylem transpiration stream. Recent studies have revealed that CLE and CEP peptides secreted in the roots are transported to above ground via the xylem in response to plant–microbe interaction and soil nitrogen starvation, respectively. Their leucine-rich repeat transmembrane receptors localized in the shoot phloem are required for relaying the signal from the shoot to the root. These findings well-fit to the current scenario of root-to-shoot-to-root feedback signaling, where peptide transport achieves the root-to-shoot signaling, the first half of the signaling process. Meanwhile, it is now well-evidenced that proteins and a range of RNAs are transported via the phloem translocation system, and some of those can exert their physiological functions at their destinations, including roots. Thus, plant vascular systems may serve not only as conduits for the translocation of essential substances but also as long-distance communication pathways that allow plants to adapt to changes in internal and external environments at the whole plant level. PMID:25852714

  2. Dynamic facial expressions of emotion transmit an evolving hierarchy of signals over time.

    PubMed

    Jack, Rachael E; Garrod, Oliver G B; Schyns, Philippe G

    2014-01-20

    Designed by biological and social evolutionary pressures, facial expressions of emotion comprise specific facial movements to support a near-optimal system of signaling and decoding. Although highly dynamical, little is known about the form and function of facial expression temporal dynamics. Do facial expressions transmit diagnostic signals simultaneously to optimize categorization of the six classic emotions, or sequentially to support a more complex communication system of successive categorizations over time? Our data support the latter. Using a combination of perceptual expectation modeling, information theory, and Bayesian classifiers, we show that dynamic facial expressions of emotion transmit an evolving hierarchy of "biologically basic to socially specific" information over time. Early in the signaling dynamics, facial expressions systematically transmit few, biologically rooted face signals supporting the categorization of fewer elementary categories (e.g., approach/avoidance). Later transmissions comprise more complex signals that support categorization of a larger number of socially specific categories (i.e., the six classic emotions). Here, we show that dynamic facial expressions of emotion provide a sophisticated signaling system, questioning the widely accepted notion that emotion communication is comprised of six basic (i.e., psychologically irreducible) categories, and instead suggesting four.

  3. Velocity measurements of heterogeneous RBC flow in capillary vessels using dynamic laser speckle signal

    NASA Astrophysics Data System (ADS)

    Li, Chenxi; Wang, Ruikang

    2017-04-01

    We propose an approach to measure heterogeneous velocities of red blood cells (RBCs) in capillary vessels using full-field time-varying dynamic speckle signals. The approach utilizes a low coherent laser speckle imaging system to record the instantaneous speckle pattern, followed by an eigen-decomposition-based filtering algorithm to extract dynamic speckle signal due to the moving RBCs. The velocity of heterogeneous RBC flows is determined by cross-correlating the temporal dynamic speckle signals obtained at adjacent locations. We verify the approach by imaging mouse pinna in vivo, demonstrating its capability for full-field RBC flow mapping and quantifying flow pattern with high resolution. It is expected to investigate the dynamic action of RBCs flow in capillaries under physiological changes.

  4. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals.

    PubMed

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-20

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector's false alarms.

  5. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression

    PubMed Central

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E.; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-01-01

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA–RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits. PMID:25916845

  6. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression.

    PubMed

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-05-26

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.

  7. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals

    PubMed Central

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-01

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector’s false alarms. PMID:26805837

  8. Analysis of Dynamic Stall Through Chirp Signal Pitch Excursions

    NASA Astrophysics Data System (ADS)

    Heintz, Kyle; Coleman, Dustin; Wicks, Michael; Corke, Thomas; Thomas, Flint

    2013-11-01

    An augmentation of the typical pitching airfoil experiment has been performed where the pitching frequency and amplitude are dynamically varied in a short-time event to produce a ``chirp'' trajectory, α (t) =α0 +α1 (t) sin (tω (t)) . The frequency evolution followed a Schroeder-phase relation, ω (t) =ωmin + K (ωmax -ωmin) . The frequencies ranged from 0.5 Hz to 30 Hz, resulting in reduced frequencies from 0.02 to 0.1. The free-stream Mach number ranged from Mach 0.4 to 0.6, giving chord Reynolds numbers from 5 ×105 to 3 ×106 . The airfoil was a NACA 23012 section shape that was fully instrumented with 31 flush-mounted high-bandwidth pressure transducers. The pressure transducer outputs were simultaneously sampled with the instantaneous angle of attack, α (t) . The motivation for this study was to compare dynamic stall under non-equilibrium conditions. A particular interest is on the flow features that occur when dynamically passing between light and deep stall regimes. The results include phase analysis of aerodynamic loads, wavelet-based spectral analysis, and the determination of the intra-cycle aerodynamic damping factors.

  9. Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.

    PubMed

    Toettcher, Jared E; Weiner, Orion D; Lim, Wendell A

    2013-12-05

    The complex, interconnected architecture of cell-signaling networks makes it challenging to disentangle how cells process extracellular information to make decisions. We have developed an optogenetic approach to selectively activate isolated intracellular signaling nodes with light and use this method to follow the flow of information from the signaling protein Ras. By measuring dose and frequency responses in single cells, we characterize the precision, timing, and efficiency with which signals are transmitted from Ras to Erk. Moreover, we elucidate how a single pathway can specify distinct physiological outcomes: by combining distinct temporal patterns of stimulation with proteomic profiling, we identify signaling programs that differentially respond to Ras dynamics, including a paracrine circuit that activates STAT3 only after persistent (>1 hr) Ras activation. Optogenetic stimulation provides a powerful tool for analyzing the intrinsic transmission properties of pathway modules and identifying how they dynamically encode distinct outcomes.

  10. Kinetics and dynamics in the G protein-coupled receptor signaling cascade.

    PubMed

    Vilardaga, Jean-Pierre; Romero, Guillermo; Feinstein, Timothy N; Wehbi, Vanessa L

    2013-01-01

    We describe optical and microscopy methods based on Förster resonance energy transfer, fluorescence recovery after photobleaching, and imaging cross-correlation spectroscopy that permit to determine kinetic and dynamic properties of key reactions involved G protein-coupled receptor (GPCR) signaling from the initial ligand binding step to the generation of the second messenger, cAMP. Well suited to determine rate-limiting reactions taking place along a GPCR signaling cascade in live cells, these techniques have also uncovered new concepts in GPCR signaling as well as many interesting mechanistic subtleties by which GPCRs transmit neurotransmitter and hormone signals into cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Detection of chaotic dynamics in human gait signals from mobile devices

    NASA Astrophysics Data System (ADS)

    DelMarco, Stephen; Deng, Yunbin

    2017-05-01

    The ubiquity of mobile devices offers the opportunity to exploit device-generated signal data for biometric identification, health monitoring, and activity recognition. In particular, mobile devices contain an Inertial Measurement Unit (IMU) that produces acceleration and rotational rate information from the IMU accelerometers and gyros. These signals reflect motion properties of the human carrier. It is well-known that the complexity of bio-dynamical systems gives rise to chaotic dynamics. Knowledge of chaotic properties of these systems has shown utility, for example, in detecting abnormal medical conditions and neurological disorders. Chaotic dynamics has been found, in the lab, in bio-dynamical systems data such as electrocardiogram (heart), electroencephalogram (brain), and gait data. In this paper, we investigate the following question: can we detect chaotic dynamics in human gait as measured by IMU acceleration and gyro data from mobile phones? To detect chaotic dynamics, we perform recurrence analysis on real gyro and accelerometer signal data obtained from mobile devices. We apply the delay coordinate embedding approach from Takens' theorem to reconstruct the phase space trajectory of the multi-dimensional gait dynamical system. We use mutual information properties of the signal to estimate the appropriate delay value, and the false nearest neighbor approach to determine the phase space embedding dimension. We use a correlation dimension-based approach together with estimation of the largest Lyapunov exponent to make the chaotic dynamics detection decision. We investigate the ability to detect chaotic dynamics for the different one-dimensional IMU signals, across human subject and walking modes, and as a function of different phone locations on the human carrier.

  12. Dynamical system modeling via signal reduction and neural network simulation

    SciTech Connect

    Paez, T.L.; Hunter, N.F.

    1997-11-01

    Many dynamical systems tested in the field and the laboratory display significant nonlinear behavior. Accurate characterization of such systems requires modeling in a nonlinear framework. One construct forming a basis for nonlinear modeling is that of the artificial neural network (ANN). However, when system behavior is complex, the amount of data required to perform training can become unreasonable. The authors reduce the complexity of information present in system response measurements using decomposition via canonical variate analysis. They describe a method for decomposing system responses, then modeling the components with ANNs. A numerical example is presented, along with conclusions and recommendations.

  13. Requirements for implementation of Kuessner and Wagner indicial lift growth functions into the FLEXSTAB computer program system for use in dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Miller, R. D.; Rogers, J. T.

    1975-01-01

    General requirements for dynamic loads analyses are described. The indicial lift growth function unsteady subsonic aerodynamic representation is reviewed, and the FLEXSTAB CPS is evaluated with respect to these general requirements. The effects of residual flexibility techniques on dynamic loads analyses are also evaluated using a simple dynamic model.

  14. Calculation of intravascular signal in dynamic contrast enhanced-MRI using adaptive complex independent component analysis.

    PubMed

    Mehrabian, Hatef; Chopra, Rajiv; Martel, Anne L

    2013-04-01

    Assessing tumor response to therapy is a crucial step in personalized treatments. Pharmacokinetic (PK) modeling provides quantitative information about tumor perfusion and vascular permeability that are associated with prognostic factors. A fundamental step in most PK analyses is calculating the signal that is generated in the tumor vasculature. This signal is usually inseparable from the extravascular extracellular signal. It was shown previously using in vivo and phantom experiments that independent component analysis (ICA) is capable of calculating the intravascular time-intensity curve in dynamic contrast enhanced (DCE)-MRI. A novel adaptive complex independent component analysis (AC-ICA) technique is developed in this study to calculate the intravascular time-intensity curve and separate this signal from the DCE-MR images of tumors. The use of the complex-valued DCE-MRI images rather than the commonly used magnitude images satisfied the fundamental assumption of ICA, i.e., linear mixing of the sources. Using an adaptive cost function in ICA through estimating the probability distribution of the tumor vasculature at each iteration resulted in a more robust and accurate separation algorithm. The AC-ICA algorithm provided a better estimate for the intravascular time-intensity curve than the previous ICA-based method. A simulation study was also developed in this study to realistically simulate DCE-MRI data of a leaky tissue mimicking phantom. The passage of the MR contrast agent through the leaky phantom was modeled with finite element analysis using a diffusion model. Once the distribution of the contrast agent in the imaging field of view was calculated, DCE-MRI data was generated by solving the Bloch equation for each voxel at each time point. The intravascular time-intensity curve calculation results were compared to the previously proposed ICA-based intravascular time-intensity curve calculation method that applied ICA to the magnitude of the DCE-MRI data

  15. Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome

    PubMed Central

    Oliveira, Ana Paula; Dimopoulos, Sotiris; Busetto, Alberto Giovanni; Christen, Stefan; Dechant, Reinhard; Falter, Laura; Haghir Chehreghani, Morteza; Jozefczuk, Szymon; Ludwig, Christina; Rudroff, Florian; Schulz, Juliane Caroline; González, Asier; Soulard, Alexandre; Stracka, Daniele; Aebersold, Ruedi; Buhmann, Joachim M; Hall, Michael N; Peter, Matthias; Sauer, Uwe; Stelling, Jörg

    2015-01-01

    Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re-wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes. PMID:25888284

  16. Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome.

    PubMed

    Oliveira, Ana Paula; Dimopoulos, Sotiris; Busetto, Alberto Giovanni; Christen, Stefan; Dechant, Reinhard; Falter, Laura; Haghir Chehreghani, Morteza; Jozefczuk, Szymon; Ludwig, Christina; Rudroff, Florian; Schulz, Juliane Caroline; González, Asier; Soulard, Alexandre; Stracka, Daniele; Aebersold, Ruedi; Buhmann, Joachim M; Hall, Michael N; Peter, Matthias; Sauer, Uwe; Stelling, Jörg

    2015-04-17

    Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re-wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Nonlinear dynamics approach to speech detection in noisy signals

    NASA Astrophysics Data System (ADS)

    Bronakowski, Lukasz J.

    2009-06-01

    The presented paper describes a novel approach to detection of speech corrupted by noise. The proposed procedure is based on fractal dimension, which is being evaluated directly from speech signal samples using two different methods: box-counting and the approach proposed by Katz. The recordings, taken from TIMIT database, were corrupted by five different types of noise (white, pink, hf-channel, babble and factory) with four noise amplitudes (5,10,15,20 dB). The resulting noisy speech was the subject of the analysis. The Otsu's method was used to determine a threshold value for differentiating between noise-only and noisy-speech segments. It has been shown that fractal dimension-based approach provides good basis for detecting speech under a presence of noise.

  18. MANIFOLD LEARNING FOR ANALYSIS OF LOW-ORDER NONLINEAR DYNAMICS IN HIGH-DIMENSIONAL ELECTROCARDIOGRAPHIC SIGNALS.

    PubMed

    Erem, B; Stovicek, P; Brooks, D H

    2012-07-12

    The dynamical structure of electrical recordings from the heart or torso surface is a valuable source of information about cardiac physiological behavior. In this paper, we use an existing data-driven technique for manifold identification to reveal electrophysiologically significant changes in the underlying dynamical structure of these signals. Our results suggest that this analysis tool characterizes and differentiates important parameters of cardiac bioelectric activity through their dynamic behavior, suggesting the potential to serve as an effective dynamic constraint in the context of inverse solutions.

  19. Characterizing the Response of Commercial and Industrial Facilities to Dynamic Pricing Signals from the Utility

    SciTech Connect

    Mathieu, Johanna L.; Gadgil, Ashok J.; Callaway, Duncan S.; Price, Phillip N.; Kiliccote, Sila

    2010-07-01

    We describe a method to generate statistical models of electricity demand from Commercial and Industrial (C&I) facilities including their response to dynamic pricing signals. Models are built with historical electricity demand data. A facility model is the sum of a baseline demand model and a residual demand model; the latter quantifies deviations from the baseline model due to dynamic pricing signals from the utility. Three regression-based baseline computation methods were developed and analyzed. All methods performed similarly. To understand the diversity of facility responses to dynamic pricing signals, we have characterized the response of 44 C&I facilities participating in a Demand Response (DR) program using dynamic pricing in California (Pacific Gas and Electric's Critical Peak Pricing Program). In most cases, facilities shed load during DR events but there is significant heterogeneity in facility responses. Modeling facility response to dynamic price signals is beneficial to the Independent System Operator for scheduling supply to meet demand, to the utility for improving dynamic pricing programs, and to the customer for minimizing energy costs.

  20. Dynamic Routing of Task-relevant Signals for Decision Making in Dorsolateral Prefrontal Cortex

    PubMed Central

    Donahue, Christopher H.; Lee, Daeyeol

    2017-01-01

    Neurons in the dorsolateral prefrontal cortex (DLPFC) encode a diverse array of sensory and mnemonic signals, but little is known about how this information is dynamically routed during decision making. We analyzed the neuronal activity in the DLPFC of monkeys performing a probabilistic reversal task where information about the probability and magnitude of reward was provided by the target color and numerical cues, respectively. The location of the target of a given color was randomized across trials, and therefore was not relevant for subsequent choices. DLPFC neurons encoded signals related to both task-relevant and irrelevant features, and task-relevant mnemonic signals were encoded congruently with choice signals. Furthermore, only the task-relevant signals related to previous events were more robustly encoded following rewarded outcomes. Thus, multiple types of neural signals are flexibly routed in the DLPFC so as to favor actions that maximize reward. PMID:25581364

  1. Spatio-temporal dynamics of a cell signal pathway with negative feedbacks: the MAPK/ERK pathway.

    PubMed

    Maya-Bernal, José Luis; Ramírez-Santiago, Guillermo

    2016-03-01

    We studied the spatio-temporal dynamics of a cell signal cascade with negative feedback that quantitatively emulates the regulative process that occurs in the Mitogen Activated Protein Kinase/Extracellular Regulated Kinase (MAPK/ERK) pathway. The model consists of a set of six coupled reaction-diffusion equations that describes the dynamics of the six-module pathway. In the basic module the active form of the protein transmits the signal to the next pathway’s module. As suggested by experiments, the model considers that the fifth module's kinase down-regulates the first and third modules. The feedback parameter is defined as, μ(r)( j)= k(kin)5/k(kin)(j), (j = 1, 3). We analysed the pathway's dynamics for μ(r)( j) = 0.10, 1.0, and 10 in the kinetic regimes: i) saturation of both kinases and phosphatases, ii) saturation of the phosphatases and iii) saturation of the kinases. For a regulated pathway the Total Activated Protein Profiles (TAPPs) as a function of time develop a maximum during the transient stage in the three kinetic regimes. These maxima become higher and their positions shift to longer times downstream. This scenario also applies to the TAPP's regulatory kinase that sums up its inhibitory action to that of the phosphatases leading to a maximum. Nevertheless, when μ(r)(j)= 1.0 , the TAPPs develop two maxima, with the second maximum being almost imperceptible. These results are in qualitative agreement with experimental data obtained from NIH 3T3 mouse fibroblasts. In addition, analyses of the stationary states as a function of position indicate that in the kinetic regime i) which is of physiological interest, signal transduction occurs with a relatively large propagation length for the three values of the regulative parameter. However, for μ(r)(j)= 0.10 , the sixth module concentration profile is transmitted with approximately 45% of its full value. The results obtained for μ(r)(j) = 10 , indicate that the first five concentration profiles are

  2. A divergent canonical WNT-signaling pathway regulates microtubule dynamics

    PubMed Central

    Ciani, Lorenza; Krylova, Olga; Smalley, Matthew J.; Dale, Trevor C.; Salinas, Patricia C.

    2004-01-01

    Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability. PMID:14734535

  3. Performance Analysis of Control Signal Transmission Technique for Cognitive Radios in Dynamic Spectrum Access Networks

    NASA Astrophysics Data System (ADS)

    Sakata, Ren; Tomioka, Tazuko; Kobayashi, Takahiro

    When cognitive radio (CR) systems dynamically use the frequency band, a control signal is necessary to indicate which carrier frequencies are currently available in the network. In order to keep efficient spectrum utilization, this control signal also should be transmitted based on the channel conditions. If transmitters dynamically select carrier frequencies, receivers have to receive control signals without knowledge of their carrier frequencies. To enable such transmission and reception, this paper proposes a novel scheme called DCPT (Differential Code Parallel Transmission). With DCPT, receivers can receive low-rate information with no knowledge of the carrier frequencies. The transmitter transmits two signals whose carrier frequencies are spaced by a predefined value. The absolute values of the carrier frequencies can be varied. When the receiver acquires the DCPT signal, it multiplies the signal by a frequency-shifted version of the signal; this yields a DC component that represents the data signal which is then demodulated. The performance was evaluated by means of numerical analysis and computer simulation. We confirmed that DCPT operates successfully even under severe interference if its parameters are appropriately configured.

  4. Signal Processing for Determining Water Height in Steam Pipes with Dynamic Surface Conditions

    NASA Technical Reports Server (NTRS)

    Lih, Shyh-Shiuh; Lee, Hyeong Jae; Bar-Cohen, Yoseph

    2015-01-01

    An enhanced signal processing method based on the filtered Hilbert envelope of the auto-correlation function of the wave signal has been developed to monitor the height of condensed water through the steel wall of steam pipes with dynamic surface conditions. The developed signal processing algorithm can also be used to estimate the thickness of the pipe to determine the cut-off frequency for the low pass filter frequency of the Hilbert Envelope. Testing and analysis results by using the developed technique for dynamic surface conditions are presented. A multiple array of transducers setup and methodology are proposed for both the pulse-echo and pitch-catch signals to monitor the fluctuation of the water height due to disturbance, water flow, and other anomaly conditions.

  5. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling.

    PubMed

    Mattila, Pieta K; Batista, Facundo D; Treanor, Bebhinn

    2016-02-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival.

  6. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

    PubMed Central

    Mattila, Pieta K.; Batista, Facundo D.

    2016-01-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

  7. Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

    PubMed Central

    Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R.; Vincent, Katy; Missmer, Stacey A.; Becker, Christian; Morris, Andrew P.; Montgomery, Grant W.

    2017-01-01

    Abstract STUDY QUESTION Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. WHAT IS KNOWN ALREADY Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. STUDY DESIGN, SIZE, DURATION Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. PARTICIPANTS/MATERIALS, SETTING, METHODS The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software

  8. Aeroelastic and dynamic finite element analyses of a bladder shrouded disk

    NASA Technical Reports Server (NTRS)

    Smith, G. C. C.; Elchuri, V.

    1980-01-01

    The delivery and demonstration of a computer program for the analysis of aeroelastic and dynamic properties is reported. Approaches to flutter and forced vibration of mistuned discs, and transient aerothermoelasticity are described.

  9. Dynamic Range Enhancement of High-Speed Electrical Signal Data via Non-Linear Compression

    NASA Technical Reports Server (NTRS)

    Laun, Matthew C. (Inventor)

    2016-01-01

    Systems and methods for high-speed compression of dynamic electrical signal waveforms to extend the measuring capabilities of conventional measuring devices such as oscilloscopes and high-speed data acquisition systems are discussed. Transfer function components and algorithmic transfer functions can be used to accurately measure signals that are within the frequency bandwidth but beyond the voltage range and voltage resolution capabilities of the measuring device.

  10. Integrated Strategies to Gain a Systems-Level View of Dynamic Signaling Networks.

    PubMed

    Newman, Robert H; Zhang, Jin

    2017-01-01

    In order to survive and function properly in the face of an ever changing environment, cells must be able to sense changes in their surroundings and respond accordingly. Cells process information about their environment through complex signaling networks composed of many discrete signaling molecules. Individual pathways within these networks are often tightly integrated and highly dynamic, allowing cells to respond to a given stimulus (or, as is typically the case under physiological conditions, a combination of stimuli) in a specific and appropriate manner. However, due to the size and complexity of many cellular signaling networks, it is often difficult to predict how cellular signaling networks will respond under a particular set of conditions. Indeed, crosstalk between individual signaling pathways may lead to responses that are nonintuitive (or even counterintuitive) based on examination of the individual pathways in isolation. Therefore, to gain a more comprehensive view of cell signaling processes, it is important to understand how signaling networks behave at the systems level. This requires integrated strategies that combine quantitative experimental data with computational models. In this chapter, we first examine some of the progress that has recently been made toward understanding the systems-level regulation of cellular signaling networks, with a particular emphasis on phosphorylation-dependent signaling networks. We then discuss how genetically targetable fluorescent biosensors are being used together with computational models to gain unique insights into the spatiotemporal regulation of signaling networks within single, living cells.

  11. A dynamic scanning method based on signal-statistics for scanning electron microscopy.

    PubMed

    Timischl, F

    2014-01-01

    A novel dynamic scanning method for noise reduction in scanning electron microscopy and related applications is presented. The scanning method dynamically adjusts the scanning speed of the electron beam depending on the statistical behavior of the detector signal and gives SEM images with uniform and predefined standard deviation, independent of the signal value itself. In the case of partially saturated images, the proposed method decreases image acquisition time without sacrificing image quality. The effectiveness of the proposed method is shown and compared to the conventional scanning method and median filtering using numerical simulations.

  12. Dynamic modes of microwave signal autogeneration in a radio photonic ring generator

    NASA Astrophysics Data System (ADS)

    Kondrashov, A. V.; Ustinov, A. B.; Kalinikos, B. A.

    2017-02-01

    Dynamic modes of microwave signal autogeneration in a radio photonic generator have been investigated. The generator is a ring circuit with a low-pass filter and microwave amplifier in its microwave path. The optical path contains an optical fiber delay line. The generator demonstrates the periodical, chaotic, and noise dynamics. It has been shown that the correlation dimensionality of the random signal attractor in the chaotic generation mode saturates with increasing phase space dimensionality. Saturation is not observed in the noise-generation mode.

  13. Transmembrane signaling of chemotaxis receptor tar: insights from molecular dynamics simulation studies.

    PubMed

    Park, Hahnbeom; Im, Wonpil; Seok, Chaok

    2011-06-22

    Transmembrane signaling of chemotaxis receptors has long been studied, but how the conformational change induced by ligand binding is transmitted across the bilayer membrane is still elusive at the molecular level. To tackle this problem, we carried out a total of 600-ns comparative molecular dynamics simulations (including model-building simulations) of the chemotaxis aspartate receptor Tar (a part of the periplasmic domain/transmembrane domain/HAMP domain) in explicit lipid bilayers. These simulations reveal valuable insights into the mechanistic picture of Tar transmembrane signaling. The piston-like movement of a transmembrane helix induced by ligand binding on the periplasmic side is transformed into a combination of both longitudinal and transversal movements of the helix on the cytoplasmic side as a result of different protein-lipid interactions in the ligand-off and ligand-on states of the receptor. This conformational change alters the dynamics and conformation of the HAMP domain, which is presumably a mechanism to deliver the signal from the transmembrane domain to the cytoplasmic domain. The current results are consistent with the previously suggested dynamic bundle model in which the HAMP dynamics change is a key to the signaling. The simulations provide further insights into the conformational changes relevant to the HAMP dynamics changes in atomic detail. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Context-dependent dynamic UV signaling in female three spine sticklebacks.

    PubMed

    Hiermes, Meike; Bakker, Theo C M; Mehlis, Marion; Rick, Ingolf P

    2015-12-10

    Color signals, including ultraviolet (UV) signals, are widespread throughout the animal kingdom and color changes can be influenced by reproductive and motivational state. However, studies on dynamic changes of UV signals are scarce. Three spine sticklebacks (Gasterosteus aculeatus) that show intraspecific UV communication were used to study dynamic UV signaling in females. Reflectance measurements were taken from the distended abdomen, which serves as signal of female fecundity and readiness to spawn for courting males, and the melanized dorsal region. Scans were taken during egg maturation as well as before and after stimulation with a male to investigate context-dependent color changes. We used a physiological model of vision to determine how females might be perceived by conspecifics and quantified chromatic contrasts among both body regions and between body regions and the background for all stages. Females showed a significant increase in abdominal UV intensity during egg maturation and in response to a courting male. Measures of chromatic contrast among body regions (abdomen vs. dorsal region) and against the background (abdomen vs. background) were also increased during egg maturation and in response to the male stimulus (abdomen vs. background). Our results provide evidence for dynamic UV signaling in females in a reproductive context.

  15. Context-dependent dynamic UV signaling in female three spine sticklebacks

    PubMed Central

    Hiermes, Meike; Bakker, Theo C. M.; Mehlis, Marion; Rick, Ingolf P.

    2015-01-01

    Color signals, including ultraviolet (UV) signals, are widespread throughout the animal kingdom and color changes can be influenced by reproductive and motivational state. However, studies on dynamic changes of UV signals are scarce. Three spine sticklebacks (Gasterosteus aculeatus) that show intraspecific UV communication were used to study dynamic UV signaling in females. Reflectance measurements were taken from the distended abdomen, which serves as signal of female fecundity and readiness to spawn for courting males, and the melanized dorsal region. Scans were taken during egg maturation as well as before and after stimulation with a male to investigate context-dependent color changes. We used a physiological model of vision to determine how females might be perceived by conspecifics and quantified chromatic contrasts among both body regions and between body regions and the background for all stages. Females showed a significant increase in abdominal UV intensity during egg maturation and in response to a courting male. Measures of chromatic contrast among body regions (abdomen vs. dorsal region) and against the background (abdomen vs. background) were also increased during egg maturation and in response to the male stimulus (abdomen vs. background). Our results provide evidence for dynamic UV signaling in females in a reproductive context. PMID:26658986

  16. Extracting protein dynamics information from overlapped NMR signals using relaxation dispersion difference NMR spectroscopy.

    PubMed

    Konuma, Tsuyoshi; Harada, Erisa; Sugase, Kenji

    2015-12-01

    Protein dynamics plays important roles in many biological events, such as ligand binding and enzyme reactions. NMR is mostly used for investigating such protein dynamics in a site-specific manner. Recently, NMR has been actively applied to large proteins and intrinsically disordered proteins, which are attractive research targets. However, signal overlap, which is often observed for such proteins, hampers accurate analysis of NMR data. In this study, we have developed a new methodology called relaxation dispersion difference that can extract conformational exchange parameters from overlapped NMR signals measured using relaxation dispersion spectroscopy. In relaxation dispersion measurements, the signal intensities of fluctuating residues vary according to the Carr-Purcell-Meiboon-Gill pulsing interval, whereas those of non-fluctuating residues are constant. Therefore, subtraction of each relaxation dispersion spectrum from that with the highest signal intensities, measured at the shortest pulsing interval, leaves only the signals of the fluctuating residues. This is the principle of the relaxation dispersion difference method. This new method enabled us to extract exchange parameters from overlapped signals of heme oxygenase-1, which is a relatively large protein. The results indicate that the structural flexibility of a kink in the heme-binding site is important for efficient heme binding. Relaxation dispersion difference requires neither selectively labeled samples nor modification of pulse programs; thus it will have wide applications in protein dynamics analysis.

  17. Predicting the evolutionary dynamic behavior of a laser with injected signal using Lyapunov exponents

    NASA Astrophysics Data System (ADS)

    Bandy, D. K.; Hall, J. R.; Denker, M. E.

    2015-07-01

    We show that the role of the Lyapunov exponents can be extended beyond the customary local instability, such as limit cycle behavior, to include its use as an evolutionary predictor of the dynamics of a laser with injected signal (LIS). Numerical studies of LIS reveal that as a function of the input-signal strength the evolution of two nonzero Lyapunov exponents (generally equal) distinctively predicts the evolutionary trend of the fundamental frequency of the laser output signal (an important dynamic characteristic of the LIS) even with the presence of some noise. This globally predictive behavior of the Lyapunov exponents includes also the dynamic behavior of the individual coexisting attractors. Different coexisting attractors of LIS and configurations of Lyapunov exponents for both individual attractors and the global system are reported. Two LIS case studies are considered: (I) a high-gain system with a rich history of nonlinear behavior but not experimentally accessible, and (II) a low-gain system that has complex dynamics and is experimentally accessible for Class B lasers. Universality arguments support the thesis that these different configurations and the extended role of the Lyapunov exponents as an evolutionary predictor of the dynamics will be observed in other nonlinear, dynamic dissipative systems as well.

  18. Nonlinear dynamic behavior of the human knee joint--Part I: Postmortem frequency domain analyses.

    PubMed

    Dortmans, L; Jans, H; Sauren, A; Huson, A

    1991-11-01

    Characteristics results of postmortem experiments on five knee-joint specimens are reported. The experiments were performed to investigate the applicability of a local linearization technique that would make it possible to describe the dynamic behavior of the joint in terms of transfer functions. The results indicate that the stiffness of the bracing wires, attached to muscle tendons to create a static equilibrium position, can be accounted for when determining the stiffness of the joint. Besides the static equilibrium configuration, the magnitude of the dynamic load and the type of dynamic load applied to the joint can be shown to have their influence. As the influence of the dynamic load is significant, it has to be concluded that in essence the knee joint has to be regarded as a nonlinear system, making application of a Local Linearization Technique questionable. However, when the magnitude of the dynamic load is included as an additional measurement parameter, an indication can be obtained about the behavior of the joint and the degree of nonlinearity.

  19. Dynamic interactions mediated by nonredundant signaling mechanisms couple circadian clock neurons.

    PubMed

    Evans, Jennifer A; Leise, Tanya L; Castanon-Cervantes, Oscar; Davidson, Alec J

    2013-11-20

    Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these signaling mechanisms, we developed a functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with similar peak times, but will peak 6-12 hr apart after in vivo exposure to long days. Once they are removed from these conditions, SCN neurons resynchronize through a phase-dependent coupling process mediated by both vasoactive intestinal polypeptide (VIP) and GABAA signaling. Notably, GABAA signaling contributes to coupling when the SCN network is in an antiphase configuration, but opposes synchrony under steady-state conditions. Further, VIP acts together with GABAA signaling to couple the network in an antiphase configuration, but promotes synchrony under steady-state conditions by counteracting the actions of GABAA signaling. Thus, SCN neurons interact through nonredundant coupling mechanisms influenced by the state of the network.

  20. Correlation of ground tests and analyses of a dynamically scaled Space Station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  1. European Space Agency's launcher multibody dynamics simulator used for system and subsystem level analyses

    NASA Astrophysics Data System (ADS)

    Baldesi, Gianluigi; Toso, Mario

    2012-06-01

    Virtual simulation is currently a key activity in the specification, design, verification and operations of space systems. System modelling and simulation support in fact a number of use cases across the spacecraft development life cycle, including activities such as system design validation, software verification and validation, spacecraft unit and sub-system test activities, etc. As the reliance on virtual modelling, simulation and justification has substantially grown in recent years, a more coordinated and consistent approach to the development of such simulation tools across project phases can bring substantial benefit in reducing the overall space programme schedule, risk and cost. By capitalizing on the ESA (European Space Agency) Structures and Mechanisms division's strong expertise in dynamics (multibody software), a generic multibody flight simulator was created to simulate a wide variety of launch vehicle dynamics and control problems at system level since 2001. The backbone of the multibody dynamics simulator is DCAP (Dynamic and Control Analysis Package), a multibody software, developed by ESA together with industry, with more than 30 years heritage in space applications. This software is a suite of fast, effective computer programs that provides the user with capabilities to model, simulate and analyze the dynamics and control performances of coupled rigid and flexible structural systems subjected to possibly time-varying structural characteristics and space environmental loads. The simulator uses the formulation for the dynamics of multi-rigid/flexible-body systems based on Order( n) algorithm. This avoids the explicit computation of a global mass matrix and its inversion, and the computational burden in these schemes increases only linearly with the number n of the system's degrees of freedom. A dedicated symbolic manipulation pre-processor is then used in the coding optimization. With the implementation of dedicated interfaces to other specialised

  2. Correlation of ground tests and analyses of a dynamically scaled space station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  3. Generalized logical model based on network topology to capture the dynamical trends of cellular signaling pathways.

    PubMed

    Zhang, Fan; Chen, Haoting; Zhao, Li Na; Liu, Hui; Przytycka, Teresa M; Zheng, Jie

    2016-01-11

    Cellular responses to extracellular perturbations require signaling pathways to capture and transmit the signals. However, the underlying molecular mechanisms of signal transduction are not yet fully understood, thus detailed and comprehensive models may not be available for all the signaling pathways. In particular, insufficient knowledge of parameters, which is a long-standing hindrance for quantitative kinetic modeling necessitates the use of parameter-free methods for modeling and simulation to capture dynamic properties of signaling pathways. We present a computational model that is able to simulate the graded responses to degradations, the sigmoidal biological relationships between signaling molecules and the effects of scheduled perturbations to the cells. The simulation results are validated using experimental data of protein phosphorylation, demonstrating that the proposed model is capable of capturing the main trend of protein activities during the process of signal transduction. Compared with existing simulators, our model has better performance on predicting the state transitions of signaling networks. The proposed simulation tool provides a valuable resource for modeling cellular signaling pathways using a knowledge-based method.

  4. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis.

    PubMed

    Fu, Jiang; Hsu, Wei

    2013-04-01

    A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction. However, it is not clear whether the inductive signal of Wnt arises intradermally or intraepidermally. Whether Wnt acts as the first dermal signal to initiate hair follicle development also remains unclear. Here we report that Wnt production mediated by Gpr177, the mouse Wls ortholog, is essential for hair follicle induction. Gpr177, encoding a multipass transmembrane protein, regulates Wnt sorting and secretion. Cell type-specific abrogation of the signal reveals that only epidermal, but not dermal, production of Wnt is required. An intraepidermal Wnt signal is necessary and sufficient for hair follicle initiation. However, the subsequent development depends on reciprocal signaling crosstalk of epidermal and dermal cells. Wnt signals within the epidermis and dermis and crossing between the epidermis and dermis have distinct roles and specific functions in skin development. This study not only defines the cell type responsible for Wnt production, but also reveals a highly dynamic regulation of Wnt signaling at different steps of hair follicle morphogenesis. Our findings uncover a mechanism underlying hair follicle development orchestrated by the Wnt pathway.

  5. Stat5 Signaling Specifies Basal versus Stress Erythropoietic Responses through Distinct Binary and Graded Dynamic Modalities

    PubMed Central

    Porpiglia, Ermelinda; Hidalgo, Daniel; Koulnis, Miroslav; Tzafriri, Abraham R.; Socolovsky, Merav

    2012-01-01

    Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog) p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a “knocked-in” EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the binary and

  6. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

    PubMed

    Porpiglia, Ermelinda; Hidalgo, Daniel; Koulnis, Miroslav; Tzafriri, Abraham R; Socolovsky, Merav

    2012-08-01

    Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog) p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the binary and

  7. Ongoing Analyses of Rocket Based Combined Cycle Engines by the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Ruf, Joseph H.; Holt, James B.; Canabal, Francisco

    2001-01-01

    This paper presents the status of analyses on three Rocket Based Combined Cycle (RBCC) configurations underway in the Applied Fluid Dynamics Analysis Group (TD64). TD64 is performing computational fluid dynamics (CFD) analysis on a Penn State RBCC test rig, the proposed Draco axisymmetric RBCC engine and the Trailblazer engine. The intent of the analysis on the Penn State test rig is to benchmark the Finite Difference Navier Stokes (FDNS) code for ejector mode fluid dynamics. The Draco analysis was a trade study to determine the ejector mode performance as a function of three engine design variables. The Trailblazer analysis is to evaluate the nozzle performance in scramjet mode. Results to date of each analysis are presented.

  8. Three-dimensional imaging system for analyses of dynamic droplet impaction and deposition formation on leaves

    USDA-ARS?s Scientific Manuscript database

    A system was developed to assess the dynamic processes of droplet impact, rebound and retention on leaf surfaces with three-dimensional (3-D) images. The system components consisted of a uniform-size droplet generator, two high speed digital video cameras, a constant speed track, a leaf holder, and ...

  9. Spatial analyses of soil properties, terrain, and water dynamics in a semi-arid agricultural landscape

    USDA-ARS?s Scientific Manuscript database

    Quantification of soil-water patterns in space and time is essential for understanding soil hydrological processes and to aid land management decisions. In undulating terrain, dynamics of profile soil water can vary by landscape position in relation to terrain attributes, soil properties, and plant ...

  10. Global and local properties used as analyses tools for molecular-dynamics simulations

    NASA Astrophysics Data System (ADS)

    Bachlechner, Martina E.; Anderson, Jonas T.; Cao, Deng; Leonard, Robert H.; Owens, Eli T.; Schiffbauer, Jarrod E.; Burky, Melissa R.; Ducatman, Samuel C.; Guffey, Eric J.; Serrano Ramos2, Fernando

    2006-03-01

    Molecular dynamics simulations have been used to study mechanical failure in realistic interface materials. Averaging over the individual atoms' contributions yields local and global information including displacements, bond angles, strains, stress tensor components, and pair distribution functions. A combined analysis of global and local properties facilitates detailed insight in the mechanisms of failure, which will eventually guide on how to prevent failure of interfaces.

  11. Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated kinase signaling in Caenorhabditis elegans germline development.

    PubMed

    Lee, Min-Ho; Ohmachi, Mitsue; Arur, Swathi; Nayak, Sudhir; Francis, Ross; Church, Diane; Lambie, Eric; Schedl, Tim

    2007-12-01

    The raison d'etre of the germline is to produce oocytes and sperm that pass genetic material and cytoplasmic constituents to the next generation. To achieve this goal, many developmental processes must be executed and coordinated. ERK, the terminal MAP kinase of a number of signaling pathways, controls many aspects of development. Here we present a comprehensive analysis of MPK-1 ERK in Caenorhabditis elegans germline development. MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation, male germ cell fate specification, and a nonessential function of promoting the proliferative fate. MPK-1 also regulates multiple aspects of cell biology during oogenesis, including membrane organization and morphogenesis: organization of pachytene cells on the surface of the gonadal tube, oocyte organization and differentiation, oocyte growth control, and oocyte nuclear migration. MPK-1 activation is temporally/spatially dynamic and most processes appear to be controlled through sustained activation. MPK-1 thus may act not only in the control of individual processes but also in the coordination of contemporaneous processes and the integration of sequential processes. Knowledge of the dynamic activation and diverse functions of MPK-1 provides the foundation for identification of upstream signaling cascades responsible for region-specific activation and the downstream substrates that mediate the various processes.

  12. Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling in Caenorhabditis elegans Germline Development

    PubMed Central

    Lee, Min-Ho; Ohmachi, Mitsue; Arur, Swathi; Nayak, Sudhir; Francis, Ross; Church, Diane; Lambie, Eric; Schedl, Tim

    2007-01-01

    The raison d'etre of the germline is to produce oocytes and sperm that pass genetic material and cytoplasmic constituents to the next generation. To achieve this goal, many developmental processes must be executed and coordinated. ERK, the terminal MAP kinase of a number of signaling pathways, controls many aspects of development. Here we present a comprehensive analysis of MPK-1 ERK in Caenorhabditis elegans germline development. MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation, male germ cell fate specification, and a nonessential function of promoting the proliferative fate. MPK-1 also regulates multiple aspects of cell biology during oogenesis, including membrane organization and morphogenesis: organization of pachytene cells on the surface of the gonadal tube, oocyte organization and differentiation, oocyte growth control, and oocyte nuclear migration. MPK-1 activation is temporally/spatially dynamic and most processes appear to be controlled through sustained activation. MPK-1 thus may act not only in the control of individual processes but also in the coordination of contemporaneous processes and the integration of sequential processes. Knowledge of the dynamic activation and diverse functions of MPK-1 provides the foundation for identification of upstream signaling cascades responsible for region-specific activation and the downstream substrates that mediate the various processes. PMID:18073423

  13. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor

    PubMed Central

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-01-01

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor. PMID:26197324

  14. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor.

    PubMed

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-07-21

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor.

  15. Microtubule Dynamics in Living Root Hairs: Transient Slowing by Lipochitin Oligosaccharide Nodulation SignalsW⃞

    PubMed Central

    Vassileva, Valya N.; Kouchi, Hiroshi; Ridge, Robert W.

    2005-01-01

    The incorporation of a fusion of green fluorescent protein and tubulin-α 6 from Arabidopsis thaliana in root hairs of Lotus japonicus has allowed us to visualize and quantify the dynamic parameters of the cortical microtubules in living root hairs. Analysis of individual microtubule turnover in real time showed that only plus polymer ends contributed to overall microtubule dynamicity, exhibiting dynamic instability as the main type of microtubule behavior in Lotus root hairs. Comparison of the four standard parameters of in vivo dynamic instability—the growth rate, the disassembly rate, and the frequency of transitions from disassembly to growth (rescue) and from growth to disassembly (catastrophe)—revealed that microtubules in young root hairs were more dynamic than those in mature root hairs. Either inoculation with Mesorhizobium loti or purified M. loti lipochitin oligosaccharide signal molecules (Nod factors) significantly affected the growth rate and transition frequencies in emerging and growing root hairs, making microtubules less dynamic at a specific window after symbiotic inoculation. This response of root hair cells to rhizobial Nod factors is discussed in terms of the possible biological significance of microtubule dynamics in the early signaling events leading to the establishment and progression of the globally important Rhizobium/legume symbiosis. PMID:15863517

  16. Dynamic versus static analyses of lifting a box from the floor.

    PubMed

    Menzer, Heather M; Reiser, Raoul F

    2005-01-01

    Lifting objects from below knee height has been implicated as a source of low back pain and injury. Static models have often been used to assess forces produced in the lumbar region by lifting; however, inertial forces generated by acceleration may be significant. Therefore, the goal of this investigation was to assess differences between static and dynamic analysis methods. Sagittal plane kinematics were collected on 21 men and 22 women of college age while lifting a milk crate (men = 25 kg, women = 15 kg) from the floor to standing knuckle height on level as well as sloped (facing uphill and downhill at 10 degrees and 20 degrees) ground conditions. Both static and dynamic top-down inverse models were utilized to assess net muscular moments at L5/S1 as well as the posture of the person at the time of static max (TSM) and dynamic max (TDM) moments. The TDM moment was significantly later than the TSM in the level through uphill conditions (p < 0.001). The dynamic max moment was significantly greater than the static max moment in all conditions (p < 0.001). Torso angles at TSM exhibited a significantly greater forward lean (by < 2 degrees) in the level through uphill conditions (p < 0.001). Overall low-back curvature, hip angles, knee angles, and ankle angles were not affected by the type of model (p > 0.05), though several minor differences occurred at conditions other than the level (most dramatic in the downhill 20 degrees condition). Therefore, if moments are of interest, a dynamic model should be utilized. However, body position is very similar at TSM and TDM.

  17. Quantum dot SOA input power dynamic range improvement for differential-phase encoded signals.

    PubMed

    Vallaitis, T; Bonk, R; Guetlein, J; Hillerkuss, D; Li, J; Brenot, R; Lelarge, F; Duan, G H; Freude, W; Leuthold, J

    2010-03-15

    Experimentally we find a 10 dB input power dynamic range advantage for amplification of phase encoded signals with quantum dot SOA as compared to low-confinement bulk SOA. An analysis of amplitude and phase effects shows that this improvement can be attributed to the lower alpha-factor found in QD SOA.

  18. Network dynamics for optimal compressive-sensing input-signal recovery.

    PubMed

    Barranca, Victor J; Kovačič, Gregor; Zhou, Douglas; Cai, David

    2014-10-01

    By using compressive sensing (CS) theory, a broad class of static signals can be reconstructed through a sequence of very few measurements in the framework of a linear system. For networks with nonlinear and time-evolving dynamics, is it similarly possible to recover an unknown input signal from only a small number of network output measurements? We address this question for pulse-coupled networks and investigate the network dynamics necessary for successful input signal recovery. Determining the specific network characteristics that correspond to a minimal input reconstruction error, we are able to achieve high-quality signal reconstructions with few measurements of network output. Using various measures to characterize dynamical properties of network output, we determine that networks with highly variable and aperiodic output can successfully encode network input information with high fidelity and achieve the most accurate CS input reconstructions. For time-varying inputs, we also find that high-quality reconstructions are achievable by measuring network output over a relatively short time window. Even when network inputs change with time, the same optimal choice of network characteristics and corresponding dynamics apply as in the case of static inputs.

  19. Network dynamics for optimal compressive-sensing input-signal recovery

    NASA Astrophysics Data System (ADS)

    Barranca, Victor J.; Kovačič, Gregor; Zhou, Douglas; Cai, David

    2014-10-01

    By using compressive sensing (CS) theory, a broad class of static signals can be reconstructed through a sequence of very few measurements in the framework of a linear system. For networks with nonlinear and time-evolving dynamics, is it similarly possible to recover an unknown input signal from only a small number of network output measurements? We address this question for pulse-coupled networks and investigate the network dynamics necessary for successful input signal recovery. Determining the specific network characteristics that correspond to a minimal input reconstruction error, we are able to achieve high-quality signal reconstructions with few measurements of network output. Using various measures to characterize dynamical properties of network output, we determine that networks with highly variable and aperiodic output can successfully encode network input information with high fidelity and achieve the most accurate CS input reconstructions. For time-varying inputs, we also find that high-quality reconstructions are achievable by measuring network output over a relatively short time window. Even when network inputs change with time, the same optimal choice of network characteristics and corresponding dynamics apply as in the case of static inputs.

  20. Two-Stage Dynamic Signal Detection: A Theory of Choice, Decision Time, and Confidence

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Busemeyer, Jerome R.

    2010-01-01

    The 3 most often-used performance measures in the cognitive and decision sciences are choice, response or decision time, and confidence. We develop a random walk/diffusion theory--2-stage dynamic signal detection (2DSD) theory--that accounts for all 3 measures using a common underlying process. The model uses a drift diffusion process to account…

  1. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

    PubMed Central

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-01-01

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

  2. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    PubMed

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  3. Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks.

    PubMed

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2015-11-01

    Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large-scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks.

  4. Single-Molecule Study of Protein-Protein Interaction Dynamics in a Cell Signaling System

    SciTech Connect

    Tan, Xin; Nalbant, Perihan; Toutchkine, Alexei; Hu, Dehong; Vorpagel, Erich R.; Hahn, Klaus M.; Lu, H PETER.

    2004-01-15

    We report a combined single-molecule fluorescence and molecular dynamics (MD) simulation study of protein-protein interactions in a GTP-binding intracellular signaling protein Cdc42 in complex with a downstream effector protein WASP. A 13- kDa WASP fragment which binds only the activated GTP-loaded Cdc42 was labeled with a novel solvatochromic dye and used to probe hydrophobic interactions significant to Cdc42/WASP recognition. Our single-molecule fluorescence measurements have shown conformational fluctuations of the protein complex and suggested multiple conformational states at a wide range of time scales might be involved in protein interaction dynamics. Single-molecule experiments have revealed the dynamic disorder or protein-protein interactions within the Cdc42/WASP complex, which may be important for regulating downstream signaling events.

  5. Single-Molecule Study of Protein-Protein Interaction Dynamics in a Cell Signaling System

    SciTech Connect

    Tan, Xin; Nalbant, Perihan; Toutchkine, Alexei; Hu, Dehong; Vorpagel, Erich R.; Hahn, Klaus M.; Lu, H. Peter

    2004-01-01

    We report a study on protein-protein noncovalent interactions in an intracellular signaling protein complex, using single-molecule spectroscopy and molecular dynamics (MD) simulations. A Wiskott-Aldrich Syndrome Protein (WASP) fragment that binds only the activated intracellular signaling protein Cdc42 was labeled with a novel solvatochromic dye and used to probe hydrophobic interactions significant to Cdc42/WASP recognition. The study shows static and dynamic inhomogeneous conformational fluctuations of the protein complex that involve bound and loosely bound states. A two-coupled, two-state Markovian kinetic model is proposed for the conformational dynamics. Finally, the MD simulations explore the origin of these conformational states and associated conformational fluctuations in this protein-protein interaction system.

  6. Kinematic and dynamic analyses of the Stanford/JPL robot hand. [MACSYMA

    SciTech Connect

    Johnson, V.J.; Starr, G.P.

    1987-11-01

    This report develops the kinematic and dynamic equations for one finger of the three-fingered Stanford/JPL robot hand and documents the physical parameters needed to implement the equations. The equations can be used in control schemes for position and force control of the Stanford/JPL robot hand. The output file for the MACSYMA program is given. 4 refs., 6 figs., 1 tab.

  7. Analyses of dynamic co-contraction level in individuals with anterior cruciate ligament injury.

    PubMed

    Teixeira da Fonseca, Sergio; Silva, Paula L P; Ocarino, Juliana M; Guimaràes, Raquel B; Oliveira, Marcela T C; Lage, Cristiane A

    2004-04-01

    A complete understanding of neural mechanisms by which ligament receptors may contribute to joint stability is not well established. It has been suggested that these receptors may be involved in a neuromuscular process related to the modulation of dynamic co-contraction, as a means of guaranteeing functional joint stability. Individuals with ACL injury have diminished dynamic co-contraction. Exploratory, cross-sectional design. Ten subjects with unilateral ACL injury treated conservatively, and ten subjects without history of injury participated in the study. The co-contraction level was assessed through EMG recordings of the vastus lateralis and biceps femoris before and after a perturbation imposed on the subjects during a walking task. Subjects with ACL injury presented significantly lower co-contraction level pre-perturbation (p = 0.045) and post-perturbation (p = 0.046) than those in the control group. The bilateral decrease in muscular co-contraction presented by individuals with ACL injury suggests that ligament and joint receptors may be responsible for a bilateral dynamic increase in muscle and joint stiffness that could result in a greater joint stability. This study analyzed a neuromuscular mechanism that might contribute to the functional stability of the knee joint.

  8. Accuracy in dynamic laser speckle: optimum size of speckles for temporal and frequency analyses

    NASA Astrophysics Data System (ADS)

    Braga, Roberto A.; González-Peña, Rolando J.

    2016-12-01

    The dynamic laser-speckle phenomenon has been used as a potential tool to monitor the activity of many biological and nonbiological samples; however, a key tailoring of the experimental configuration must be taken into account to avoid wrong measurements, since the general rules addressed to speckle as information cannot be directly adopted in dynamic laser-speckle monitoring. The speckle/pixel size ratio is provided by the f-number and by the magnification of the macro lens, and attention is mainly directed toward adjusting a speckle/pixel ratio higher than 1. However, a speckle/pixel ratio much higher than one does not mean an optimum adjustment. This work tested different apertures with fixed magnification yielding to monitor a drying paint process. The outcomes were evaluated in the time and frequency domains. The highest speckle/pixel size ratio was not the best to monitor the process using the dynamic laser speckle under frequency analysis. Tailoring of the devices must take into account the optimum speckle/pixel size ratio, which could vary depending on the application, and the known Nyquist theorem cannot be considered as a sufficient condition since the setup of the optical camera with its macro and iris must also be adjusted in accordance with the frequency response.

  9. Toward global modelling approaches for dynamic analyses of rotating assemblies of turbomachines

    NASA Astrophysics Data System (ADS)

    Chatelet, Eric; D'Ambrosio, Flavio; Jacquet-Richardet, Georges

    2005-04-01

    It is now increasingly necessary to predict accurately, at the design stage and without excessive computer costs, the dynamic behavior of rotating parts of turbomachines, in order to be able to avoid resonant conditions at operating speeds. Classical approaches are based on different uncoupled models. For example, rotordynamics deals with the shaft behavior while bladed assemblies dynamics deals with wheels, and the possibility of interaction between those elements is generally not analyzed. In this study, the global non-rotating mode shapes of flexible bladed disc-shaft assemblies are used in a modal analysis method for calculating the dynamic characteristics (frequencies and mode shapes) of the corresponding rotating system. The non-rotating mode shapes are computed using a finite element cyclic symmetry approach. Rotational effects, such as centrifugal stiffening and gyroscopic effects, are accounted for. All the possible couplings between the flexible parts and every kind of deformations are allowed. The proposed model is applied to a thin-walled composite shaft and to a turbomolecular pump rotating assembly. The results obtained illustrate clearly some of the limitations of classical approaches.

  10. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    SciTech Connect

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H{sub 2}. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H{sub 2} under vapor pressure, demonstrating the difference from liquid and high-pressure solid H{sub 2}. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H{sub 2} molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H–H vibrational frequencies as well as H–H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H{sub 2} solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  11. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure.

    PubMed

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  12. Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses

    PubMed Central

    Stephen, Emily P.; Lepage, Kyle Q.; Eden, Uri T.; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S.; Guenther, Frank H.; Kramer, Mark A.

    2014-01-01

    The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295

  13. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    NASA Astrophysics Data System (ADS)

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-01

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  14. Discrete Dynamics Model for the Speract-Activated Ca2+ Signaling Network Relevant to Sperm Motility

    PubMed Central

    Espinal, Jesús; Aldana, Maximino; Guerrero, Adán; Wood, Christopher

    2011-01-01

    Understanding how spermatozoa approach the egg is a central biological issue. Recently a considerable amount of experimental evidence has accumulated on the relation between oscillations in intracellular calcium ion concentration ([Ca]) in the sea urchin sperm flagellum, triggered by peptides secreted from the egg, and sperm motility. Determination of the structure and dynamics of the signaling pathway leading to these oscillations is a fundamental problem. However, a biochemically based formulation for the comprehension of the molecular mechanisms operating in the axoneme as a response to external stimulus is still lacking. Based on experiments on the S. purpuratus sea urchin spermatozoa, we propose a signaling network model where nodes are discrete variables corresponding to the pathway elements and the signal transmission takes place at discrete time intervals according to logical rules. The validity of this model is corroborated by reproducing previous empirically determined signaling features. Prompted by the model predictions we performed experiments which identified novel characteristics of the signaling pathway. We uncovered the role of a high voltage-activated channel as a regulator of the delay in the onset of fluctuations after activation of the signaling cascade. This delay time has recently been shown to be an important regulatory factor for sea urchin sperm reorientation. Another finding is the participation of a voltage-dependent calcium-activated channel in the determination of the period of the fluctuations. Furthermore, by analyzing the spread of network perturbations we find that it operates in a dynamically critical regime. Our work demonstrates that a coarse-grained approach to the dynamics of the signaling pathway is capable of revealing regulatory sperm navigation elements and provides insight, in terms of criticality, on the concurrence of the high robustness and adaptability that the reproduction processes are predicted to have developed

  15. Dynamic vibrotactile warning signals for frontal collision avoidance: towards the torso versus towards the head.

    PubMed

    Meng, Fanxing; Ho, Cristy; Gray, Rob; Spence, Charles

    2015-01-01

    Three experiments were conducted to assess the effectiveness of dynamic vibrotactile warning signals with different spatial patterns and to compare dynamic towards-torso and towards-head vibrotactile warnings in a simulated driving task. The results revealed that embedding additional stimuli between the participant's hands and waist in the towards-torso cues (Experiment 1) and increasing the spatial distance between adjacent stimuli in the towards-head cues (Experiment 2) did not result in any further benefits in braking response times (BRTs). The triple towards-head cues resulting from the sequential operation of three pairs of stimuli on the torso gave rise to a significant advantage over the static cues; however, it did not outperform the dynamic towards-torso cues with just two pairs of stimuli. Taken together, these results demonstrated the promise of dynamic vibrotactile warnings (especially, the towards-torso warnings) in terms of the future design of more effective rear-end collision warnings. Three experiments assessed the effectiveness of dynamic towards-torso and towards-head vibrotactile warning signals in a simulated driving task. The results demonstrated the promise of dynamic vibrotactile warnings (especially, the towards-torso vibrotactile warnings) in terms of the future design of more effective frontal collision warnings.

  16. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling

    PubMed Central

    Zhou, Yong; Wong, Ching-On; Cho, Kwang-jin; van der Hoeven, Dharini; Liang, Hong; Thakur, Dhananiay P.; Luo, Jialie; Babic, Milos; Zinsmaier, Konrad E.; Zhu, Michael X.; Hu, Hongzhen; Venkatachalam, Kartik; Hancock, John F.

    2015-01-01

    Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras–dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits. PMID:26293964

  17. A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

    NASA Astrophysics Data System (ADS)

    Peter, Emanuel; Dick, Bernhard; Baeurle, Stephan A.

    2012-03-01

    Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.

  18. Dynamic characterization of a lightweight, highly maneuverable spacecraft using modal and finite element analyses

    SciTech Connect

    Manning, P.A.; Burdick, R.B.; Woehrle, T.G.

    1992-11-01

    The Lawrence Livermore National Laboratory is engaged in a technology development project which includes designing a lightweight, autonomous, highly maneuverable space vehicle, commonly referred to as a probe. The current probe design includes a guidance and control system that requires complete information on the dynamic response of the probe during operation. A finite element model of the probe was constructed to provide analytical information on the dynamic response to specific operational inputs. In order to verify the assumptions made in the model, a mass mock-up of the probe was constructed at LLNL and an experimental modal survey was performed to determine the frequencies, damping values and deflection shapes for each natural mode of the mock-up. The experimental modal parameters were compared with the parameters obtained through modal analysis of the finite element model to provide a measure of the correlation between the model and the actual structure. This report describes the experimental modal testing and analysis of the mass mock-up and compares the experimental results with the finite element results.

  19. Dynamic changes in brewing yeast cells in culture revealed by statistical analyses of yeast morphological data.

    PubMed

    Ohnuki, Shinsuke; Enomoto, Kenichi; Yoshimoto, Hiroyuki; Ohya, Yoshikazu

    2014-03-01

    The vitality of brewing yeasts has been used to monitor their physiological state during fermentation. To investigate the fermentation process, we used the image processing software, CalMorph, which generates morphological data on yeast mother cells and bud shape, nuclear shape and location, and actin distribution. We found that 248 parameters changed significantly during fermentation. Successive use of principal component analysis (PCA) revealed several important features of yeast, providing insight into the dynamic changes in the yeast population. First, PCA indicated that much of the observed variability in the experiment was summarized in just two components: a change with a peak and a change over time. Second, PCA indicated the independent and important morphological features responsible for dynamic changes: budding ratio, nucleus position, neck position, and actin organization. Thus, the large amount of data provided by imaging analysis can be used to monitor the fermentation processes involved in beer and bioethanol production. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Flow dynamics analyses of pathophysiological liver lobules using porous media theory

    NASA Astrophysics Data System (ADS)

    Hu, Jinrong; Lü, Shouqin; Feng, Shiliang; Long, Mian

    2017-08-01

    Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule, is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic, and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts (PTs) and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules. Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.

  1. The role of ecological dynamics in analysing performance in team sports.

    PubMed

    Vilar, Luís; Araújo, Duarte; Davids, Keith; Button, Chris

    2012-01-01

    Performance analysis is a subdiscipline of sports sciences and one-approach, notational analysis, has been used to objectively audit and describe behaviours of performers during different subphases of play, providing additional information for practitioners to improve future sports performance. Recent criticisms of these methods have suggested the need for a sound theoretical rationale to explain performance behaviours, not just describe them. The aim of this article was to show how ecological dynamics provides a valid theoretical explanation of performance in team sports by explaining the formation of successful and unsuccessful patterns of play, based on symmetry-breaking processes emerging from functional interactions between players and the performance environment. We offer the view that ecological dynamics is an upgrade to more operational methods of performance analysis that merely document statistics of competitive performance. In support of our arguments, we refer to exemplar data on competitive performance in team sports that have revealed functional interpersonal interactions between attackers and defenders, based on variations in the spatial positioning of performers relative to each other in critical performance areas, such as the scoring zones. Implications of this perspective are also considered for practice task design and sport development programmes.

  2. Laguerre-model blind system identification: cardiovascular dynamics estimated from multiple peripheral circulatory signals.

    PubMed

    McCombie, Devin B; Reisner, Andrew T; Asada, Haruhiko Harry

    2005-11-01

    This paper presents a method for comparing multiple circulatory waveforms measured at different locations to improve cardiovascular parameter estimation from these signals. The method identifies the distinct vascular dynamics that shape each waveform signal, and estimates the common cardiac flow input shared by them. This signal-processing algorithm uses the Laguerre function series expansion for modeling the hemodynamics of each arterial branch, and identifies unknown parameters in these models from peripheral waveforms using multichannel blind system identification. An effective technique for determining the Laguerre base pole is developed, so that the Laguerre expansion captures and quickly converges to the intrinsic arterial dynamics observed in the two circulatory signals. Furthermore, a novel deconvolution method is developed in order to stably invert the identified dynamic models for estimating the cardiac output (CO) waveform from peripheral pressure waveforms. The method is applied to experimental swine data. A mean error of less than 5% with the measured peripheral pressure waveforms has been achieved using the models and excellent agreement between the estimated CO waveforms and the gold standard measurements have been obtained.

  3. Dynamic analyses of a crack run-arrest experiment in a nonisothermal plate

    SciTech Connect

    Bass, B.R.; Pugh, C.E.; Stamm, H.K.

    1985-06-01

    In crack-arrest studies sponsored by the Heavy-Section Steel Technology (HSST) Program, a primary objective has been to produce fracture toughness data for reactor pressure vessel materials at temperatures approaching the Charpy upper-shelf regime. Wide-plate tests being conducted at the National Bureau of Standards for the HSST Program are providing an opportunity to obtain significant numbers of data points at affordable costs. In these tests, a single-edge crack in a wide-plate which is subjected to tensile loading initiates at low temperature and arrests in a region of increased fracture toughness. The gradient in toughness is achieved by applying a linear transverse temperature profile across the plate. The second test in this series for A 533 grade B class 1 steel involves crack initiation in cleavage followed by arrest at a temperature corresponding to Charpy upper-shelf behavior. The plate geometry, the material properties, and the instrumentation are discussed along with conditions and results for this test. Pretest static and elastodynamic analyses are described, and posttest analyses based on actual boundary conditions are shown to compare favorably with the observed run-arrest events.

  4. dNSP: a biologically inspired dynamic Neural network approach to Signal Processing.

    PubMed

    Cano-Izquierdo, José Manuel; Ibarrola, Julio; Pinzolas, Miguel; Almonacid, Miguel

    2008-09-01

    The arriving order of data is one of the intrinsic properties of a signal. Therefore, techniques dealing with this temporal relation are required for identification and signal processing tasks. To perform a classification of the signal according with its temporal characteristics, it would be useful to find a feature vector in which the temporal attributes were embedded. The correlation and power density spectrum functions are suitable tools to manage this issue. These functions are usually defined with statistical formulation. On the other hand, in biology there can be found numerous processes in which signals are processed to give a feature vector; for example, the processing of sound by the auditory system. In this work, the dNSP (dynamic Neural Signal Processing) architecture is proposed. This architecture allows representing a time-varying signal by a spatial (thus statical) vector. Inspired by the aforementioned biological processes, the dNSP performs frequency decomposition using an analogical parallel algorithm carried out by simple processing units. The architecture has been developed under the paradigm of a multilayer neural network, where the different layers are composed by units whose activation functions have been extracted from the theory of Neural Dynamic [Grossberg, S. (1988). Nonlinear neural networks principles, mechanisms and architectures. Neural Networks, 1, 17-61]. A theoretical study of the behavior of the dynamic equations of the units and their relationship with some statistical functions allows establishing a parallelism between the unit activations and correlation and power density spectrum functions. To test the capabilities of the proposed approach, several testbeds have been employed, i.e. the frequencial study of mathematical functions. As a possible application of the architecture, a highly interesting problem in the field of automatic control is addressed: the recognition of a controlled DC motor operating state.

  5. Descriptive and sensitivity analyses of WATBALI: A dynamic soil water model

    NASA Technical Reports Server (NTRS)

    Hildreth, W. W. (Principal Investigator)

    1981-01-01

    A soil water computer model that uses the IBM Continuous System Modeling Program III to solve the dynamic equations representing the soil, plant, and atmospheric physical or physiological processes considered is presented and discussed. Using values describing the soil-plant-atmosphere characteristics, the model predicts evaporation, transpiration, drainage, and soil water profile changes from an initial soil water profile and daily meteorological data. The model characteristics and simulations that were performed to determine the nature of the response to controlled variations in the input are described the results of the simulations are included and a change that makes the response of the model more closely represent the observed characteristics of evapotranspiration and profile changes for dry soil conditions is examined.

  6. Analysing periodicity, nonlinearity and transitional characteristics of nonlinear dynamic systems with Periodicity Ratio (PR)

    NASA Astrophysics Data System (ADS)

    Dai, L.; Han, L.

    2011-12-01

    The multiple-periodicity, nonlinearity and transitional characteristics of nonlinear dynamic systems subjected to external excitations are studied in this research. Diagnoses of the number and changing multiple-periodicities of Duffing's systems are performed with implementation of the Periodicity Ratio (PR). The multiple-periodicity diagram is generated such that the periodicities and nonlinearity of the systems with respect to the system parameters can be graphically studied. The stability and convergence of the systems are investigated. The results of the research show that the number of period of periodicity of the systems increases continuously when certain system parameters increase. Transitional characteristics of the systems are also investigated. Both Lyapunov Exponents and Periodicity Ratio are implemented to diagnose the transitional routes of the systems. New symmetrical transition characters from periodicity to quasi-periodicity and chaos are displayed in terms of PR values. Comparing to Lyapunov Exponents, the Periodicity Ratio discloses more detailed and accurate transition information.

  7. Incorporating Undrained Pore Fuid Pressurization Into Analyses of Off-Fault Plasticity During Dynamic Rupture

    NASA Astrophysics Data System (ADS)

    Viesca, R. C.; Templeton, E. L.; Rice, J. R.

    2007-12-01

    When considering dynamic fault rupture in fluid-saturated elastic-plastic materials, it is sensible to assume locally undrained behavior everywhere except in small diffusive boundary layers along the rupture surface. To evaluate undrained pore pressure changes, we consider here not just the linear poroelastic effect expressed in terms of the Skempton coefficient B, like in our previous work [Viesca et al., AGU Fall 2006], but also include plastic dilatancy, which, when positive, induces a fluid suction. We work in the context of Mohr-Coulomb-like plasticity, but with a Drucker-Prager type model. Plastic parts of strain increments are controlled by the Terzaghi effective stress, elastic parts by the Biot stress combination. Following earlier work of Rudnicki, the incremental elastic-plastic constitutive relation for undrained deformation has precisely the same form as for drained deformation, so long as we change the drained constitutive parameters into new undrained ones under transformation rules that we present. Spontaneous slip-weakening fault rupture is analyzed using the dynamic finite element procedures with ABAQUS Explicit, and undrained elastic-plastic properties. Results are shown for plastic zones and effects on rupture propagation, and how they are influenced by such parameters as B and ratio β of dilatant to shear plastic strains, for a range of principal orientations and magnitudes (relative to yield) of the pre-stress state. The undrained approximation must fail in diffusive boundary layers along the slip surface [Rudnicki and Rice, JGR 2006; Dunham and Rice, AGU Fall 2006] because the predicted pore pressures will be discontinuous at the fault. We show how to extend the Rudnicki and Rice calculation of the actual pore pressure on the fault in terms of the undrained predictions to the two sides. However, because of difficulties thus far in representing this within the ABAQUS program, all results obtained as of the time of writing neglect effects of

  8. Analysing land and vegetation cover dynamics during last three decades in Katerniaghat wildlife sanctuary, India

    NASA Astrophysics Data System (ADS)

    Chitale, V. S.; Behera, M. D.

    2014-10-01

    The change in the tropical forests could be clearly linked to the expansion of the human population and economies. An understanding of the anthropogenic forcing plays an important role in analyzing the impacts of climate change and the fate of tropical forests in the present and future scenario. In the present study, we analyze the impact of natural and anthropogenic factors in forest dynamics in Katerniaghat wildlife sanctuary situated along the Indo-Nepal border in Uttar Pradesh state, India. The study site is under tremendous pressure due to anthropogenic factors from surrounding areas since last three decades. The vegetation cover of the sanctuary primarily comprised of Shorea robusta forests, Tectona grandis plantation, and mixed deciduous forest; while the land cover comprised of agriculture, barren land, and water bodies. The classification accuracy was 83.5%, 91.5%, and 95.2% with MSS, IKONOS, and Quickbird datasets, respectively. Shorea robusta forests showed an increase of 16 km2; while Tectona grandis increased by 63.01 km2 during 1975-2010. The spatial heterogeneity in these tropical vegetation classes surrounded by the human dominated agricultural lands could not be addressed using Landsat MSS data due to coarse spatial resolution; whereas the IKONOS and Quickbird satellite datasets proved to advantageous, thus being able to precisely address the variations within the vegetation classes as well as in the land cover classes and along the edge areas. Massive deforestation during 1970s along the adjoining international boundary with Nepal has led to destruction of the wildlife corridor and has exposed the wildlife sanctuary to human interference like grazing and poaching. Higher rates of forest dynamics during the 25-year period indicate the vulnerability of the ecosystem to the natural and anthropogenic disturbances in the proximity of the sanctuary.

  9. Carotid Artery Stenosis Near a Bifurcation Investigated by Fluid Dynamic Analyses

    PubMed Central

    Filardi, V.

    2013-01-01

    Summary Haemodynamic physical parameters play a role in determining endothelial cell phenotype and influence vascular remodelling. Accurate measurement of total pressure, velocity magnitude, and wall shear stress is vital for studies on the pathogenesis of atherosclerosis. This paper investigated a lesion-based computational fluid dynamic (CFD-Fluent) pilot analysis to understand the complex haemodynamic changes prevailing in patients with high-grade carotid artery stenosis (CS) 90%. All subjects were examined with colour-flow Doppler, power Doppler, and digital subtraction angiography to enable visualization of carotid stenosis and plaque surface morphology, and used to generate computational meshes. Two models were devised: the first without any stenosis and the second with an 82% grade of stenosis localized in the external carotid artery. The distribution of the principal parameters can be obtained by computational fluid dynamics (CFD-Fluent) using patient-specific geometries and flow analytical measurements. The total pressure distribution ranged between 16,000 and 8,000 Pa in the case of normal carotid artery and 16,000 and 5,500 Pa in the case of the stenosed artery. The velocity registered a peak in the stenosis region of 5 m/s. The mean wall shear stress within the stenosis region was 360 Pa. In conclusion, patient-based CFD-Fluent analysis of CS predicts a complex haemodynamic environment with large spatial haemodynamic parameter variations that occur very rapidly over short distances. Our results improve estimates of the flow changes and forces at the vessel wall in CS and the link between haemodynamic changes and stenosis pathophysiology. PMID:24007732

  10. Beam dynamics in disordered P T -symmetric optical lattices based on eigenstate analyses

    NASA Astrophysics Data System (ADS)

    Yao, Xiankun; Liu, Xueming

    2017-03-01

    Wave functions will experience a localization process when evolving in disordered lattices. Here, we have demonstrated the effects of disordered P T -symmetric potentials on wave-function characteristics in optics based on eigenstate analyses. In weak-disorder cases, by using the tight-binding approximation method, a conclusion is obtained that the increasing of the imaginary part of potential can enhance the diffraction, while the increasing disorder will block the diffraction and lead to localization. In the general case, band theory is used for band-structure analysis of three bands. We find that the disorder has a smaller effect on the higher-order band, which is proved by the beam evolutions. Our work may be instructive for realizing beam path control by manipulating the strengths of disorder and gain and/or loss of lattice.

  11. Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports.

    PubMed

    Twomey, Deirdre M; Kelly, Simon P; O'Connell, Redmond G

    2016-07-13

    Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has

  12. Multiscale Model of Dynamic Neuromodulation Integrating Neuropeptide-Induced Signaling Pathway Activity with Membrane Electrophysiology

    PubMed Central

    Makadia, Hirenkumar K.; Anderson, Warren D.; Fey, Dirk; Sauter, Thomas; Schwaber, James S.; Vadigepalli, Rajanikanth

    2015-01-01

    We developed a multiscale model to bridge neuropeptide receptor-activated signaling pathway activity with membrane electrophysiology. Typically, the neuromodulation of biochemical signaling and biophysics have been investigated separately in modeling studies. We studied the effects of Angiotensin II (AngII) on neuronal excitability changes mediated by signaling dynamics and downstream phosphorylation of ion channels. Experiments have shown that AngII binding to the AngII receptor type-1 elicits baseline-dependent regulation of cytosolic Ca2+ signaling. Our model simulations revealed a baseline Ca2+-dependent response to AngII receptor type-1 activation by AngII. Consistent with experimental observations, AngII evoked a rise in Ca2+ when starting at a low baseline Ca2+ level, and a decrease in Ca2+ when starting at a higher baseline. Our analysis predicted that the kinetics of Ca2+ transport into the endoplasmic reticulum play a critical role in shaping the Ca2+ response. The Ca2+ baseline also influenced the AngII-induced excitability changes such that lower Ca2+ levels were associated with a larger firing rate increase. We examined the relative contributions of signaling kinases protein kinase C and Ca2+/Calmodulin-dependent protein kinase II to AngII-mediated excitability changes by simulating activity blockade individually and in combination. We found that protein kinase C selectively controlled firing rate adaptation whereas Ca2+/Calmodulin-dependent protein kinase II induced a delayed effect on the firing rate increase. We tested whether signaling kinetics were necessary for the dynamic effects of AngII on excitability by simulating three scenarios of AngII-mediated KDR channel phosphorylation: (1), an increased steady state; (2), a step-change increase; and (3), dynamic modulation. Our results revealed that the kinetics emerging from neuromodulatory activation of the signaling network were required to account for the dynamical changes in excitability. In

  13. Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports

    PubMed Central

    Twomey, Deirdre M.; Kelly, Simon P.

    2016-01-01

    Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8–16 and 18–30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. SIGNIFICANCE STATEMENT Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research

  14. Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

    PubMed Central

    Friedman, Rachel S.; Beemiller, Peter; Sorensen, Caitlin M.; Jacobelli, Jordan

    2010-01-01

    The real-time dynamics of the T cell receptor (TCR) reflect antigen detection and T cell signaling, providing valuable insight into the evolving events of the immune response. Despite considerable advances in studying TCR dynamics in simplified systems in vitro, live imaging of subcellular signaling complexes expressed at physiological densities in intact tissues has been challenging. In this study, we generated a transgenic mouse with a TCR fused to green fluorescent protein to provide insight into the early signaling events of the immune response. To enable imaging of TCR dynamics in naive T cells in the lymph node, we enhanced signal detection of the fluorescent TCR fusion protein and used volumetric masking with a second fluorophore to mark the T cells expressing the fluorescent TCR. These in vivo analyses and parallel experiments in vitro show minimal and transient incorporation of TCRs into a stable central supramolecular activating cluster (cSMAC) structure but strong evidence for rapid, antigen-dependent TCR internalization that was not contingent on T cell motility arrest or cSMAC formation. Short-lived antigen-independent TCR clustering was also occasionally observed. These in vivo observations demonstrate that varied TCR trafficking and cell arrest dynamics occur during early T cell activation. PMID:21041455

  15. Hilbert-Huang Transformation Based Analyses of FP1, FP2, and Fz Electroencephalogram Signals in Alcoholism.

    PubMed

    Lin, Chin-Feng; Su, Jiun-Yi; Wang, Hao-Min

    2015-09-01

    Chronic alcoholism may damage the central nervous system, causing imbalance in the excitation-inhibition homeostasis in the cortex, which may lead to hyper-arousal of the central nervous system, and impairments in cognitive function. In this paper, we use the Hilbert-Huang transformation (HHT) method to analyze the electroencephalogram (EEG) signals from control and alcoholic observers who watched two different pictures. We examined the intrinsic mode function (IMF) based energy distribution features of FP1, FP2, and Fz EEG signals in the time and frequency domains for alcoholics. The HHT-based characteristics of the IMFs, the instantaneous frequencies, and the time-frequency-energy distributions of the IMFs of the clinical FP1, FP2, and Fz EEG signals recorded from normal and alcoholic observers who watched two different pictures were analyzed. We observed that the number of peak amplitudes of the alcoholic subjects is larger than that of the control. In addition, the Pearson correlation coefficients of the IMFs, and the energy-IMF distributions of the clinical FP1, FP2, and Fz EEG signals recorded from normal and alcoholic observers were analyzed. The analysis results show that the energy ratios of IMF4, IMF5, and IMF7 waves of the normal observers to the refereed total energy were larger than 10 %, respectively. In addition, the energy ratios of IMF3, IMF4, and IMF5 waves of the alcoholic observers to the refereed total energy were larger than 10 %. The FP1 and FP2 waves of the normal observers, the FP1 and FP2 waves of the alcoholic observers, and the FP1 and Fz waves of the alcoholic observers demonstrated extremely high correlations. On the other hand, the FP1 waves of the normal and alcoholic observers, the FP1 wave of the normal observer and the FP2 wave of the alcoholic observer, the FP1 wave of the normal observer and the Fz wave of the alcoholic observer, the FP2 waves of the normal and alcoholic FP2 observers, and the FP2 wave of the normal observer and

  16. Detecting dynamic signals of ideally ordered nanohole patterned disk media fabricated using nanoimprint lithography

    NASA Astrophysics Data System (ADS)

    Oshima, Hirotaka; Kikuchi, Hideyuki; Nakao, Hiroshi; Itoh, Ken-ichi; Kamimura, Takuya; Morikawa, Takeshi; Matsumoto, Koji; Umada, Takahiro; Tamura, Hiroaki; Nishio, Kazuyuki; Masuda, Hideki

    2007-07-01

    The authors have fabricated ideally ordered alumina nanohole patterned disk media via anodic oxidation and nanoimprint lithography with a thermoplastic resist. The ordered arrays of alumina nanoholes with 100nm pitch, filled with Co by electrodeposition, were created over a macroscopically large area on a hard-disk substrate using these industrially applicable nanofabrication technologies. Stable flight of a perpendicular magnetic head above the media and perpendicular magnetic anisotropy of the Co nanopillars enable high-speed dynamic magnetic recording and playback. Dynamic periodic signals that matched the nanopillar periodicity were clearly observed after writing bit patterns, showing alternate reversal of magnetization of the nanopillars.

  17. Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor

    PubMed Central

    Chang, Steven D.; Mascarella, S. Wayne; Spangler, Skylar M.; Gurevich, Vsevolod V.; Navarro, Hernan A.; Carroll, F. Ivy

    2015-01-01

    Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure-activity relationship models for G protein–coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3-piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein–biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor. PMID:26134494

  18. Rosetta lander Philae: Flight Dynamics analyses for landing site selection and post-landing operations

    NASA Astrophysics Data System (ADS)

    Jurado, Eric; Martin, Thierry; Canalias, Elisabet; Blazquez, Alejandro; Garmier, Romain; Ceolin, Thierry; Gaudon, Philippe; Delmas, Cedric; Biele, Jens; Ulamec, Stephan; Remetean, Emile; Torres, Alex; Laurent-Varin, Julien; Dolives, Benoit; Herique, Alain; Rogez, Yves; Kofman, Wlodek; Jorda, Laurent; Zakharov, Vladimir; Crifo, Jean-François; Rodionov, Alexander; Heinish, P.; Vincent, Jean-Baptiste

    2016-08-01

    On the 12th of November 2014, The Rosetta Lander Philae became the first spacecraft to softly land on a comet nucleus. Due to the double failure of the cold gas hold-down thruster and the anchoring harpoons that should have fixed Philae to the surface, it spent approximately two hours bouncing over the comet surface to finally come at rest one km away from its target site. Nevertheless it was operated during the 57 h of its First Science Sequence. The FSS, performed with the two batteries, should have been followed by the Long Term Science Sequence but Philae was in a place not well illuminated and fell into hibernation. Yet, thanks to reducing distance to the Sun and to seasonal effect, it woke up at end of April and on 13th of June it contacted Rosetta again. To achieve this successful landing, an intense preparation work had been carried out mainly between August and November 2014 to select the targeted landing site and define the final landing trajectory. After the landing, the data collected during on-comet operations have been used to assess the final position and orientation of Philae, and to prepare the wake-up. This paper addresses the Flight Dynamics studies done in the scope of this landing preparation from Lander side, in close cooperation with the team at ESA, responsible for Rosetta, as well as for the reconstruction of the bouncing trajectory and orientation of the Lander after touchdown.

  19. QIN: Practical Considerations in T1 Mapping of Prostate for Dynamic Contrast Enhancement Pharmacokinetic Analyses

    PubMed Central

    Fennessy, Fiona M; Fedorov, Andriy; Gupta, Sandeep N; Schmidt, Ehud J; Tempany, Clare M; Mulkern, Robert V

    2012-01-01

    There are many challenges in developing robust imaging biomarkers that can be reliably applied in a clinical trial setting. In the case of Dynamic Contrast Enhanced (DCE) MRI, one such challenge is to obtain accurate pre-contrast T1 maps for subsequent use in two-compartment pharmacokinetic models commonly used to fit the MR enhancement time courses. In the prostate, a convenient and common approach for this task has been to use the same 3D SPGR sequence used to collect the DCE data, but with variable flip angles (VFA’s) to collect data suitable for T1 mapping prior to contrast injection. However, inhomogeneous radiofrequency conditions within the prostate have been found to adversely affect the accuracy of this technique. Herein we demonstrate the sensitivity of DCE pharmacokinetic parameters to pre-contrast T1 values and examine methods to improve the accuracy of T1 mapping with flip angle corrected VFA SPGR methods, comparing T1 maps from such methods with reference T1 maps generated with saturation recovery experiments performed with fast spin echo (FSE) sequences. PMID:22898681

  20. Computational Fluid Dynamics Analyses on Very High Temperature Reactor Air Ingress

    SciTech Connect

    Chang H Oh; Eung S. Kim; Richard Schultz; David Petti; Hyung S. Kang

    2009-07-01

    A preliminary computational fluid dynamics (CFD) analysis was performed to understand density-gradient-induced stratified flow in a Very High Temperature Reactor (VHTR) air-ingress accident. Various parameters were taken into consideration, including turbulence model, core temperature, initial air mole-fraction, and flow resistance in the core. The gas turbine modular helium reactor (GT-MHR) 600 MWt was selected as the reference reactor and it was simplified to be 2-D geometry in modeling. The core and the lower plenum were assumed to be porous bodies. Following the preliminary CFD results, the analysis of the air-ingress accident has been performed by two different codes: GAMMA code (system analysis code, Oh et al. 2006) and FLUENT CFD code (Fluent 2007). Eventually, the analysis results showed that the actual onset time of natural convection (~160 sec) would be significantly earlier than the previous predictions (~150 hours) calculated based on the molecular diffusion air-ingress mechanism. This leads to the conclusion that the consequences of this accident will be much more serious than previously expected.

  1. Dynamic path bifurcation in the Beckmann reaction: support from kinetic analyses.

    PubMed

    Yamamoto, Yutaro; Hasegawa, Hiroto; Yamataka, Hiroshi

    2011-06-03

    The reactions of oximes to amides, known as the Beckmann rearrangement, may undergo fragmentation to form carbocations + nitriles when the migrating groups have reasonable stability as cations. The reactions of oxime sulfonates of 1-substituted-phenyl-2-propanone derivatives (7-X) and related substrates (8-X, 9a-X) in aqueous CH(3)CN gave both rearrangement products (amides) and fragmentation products (alcohols), the ratio of which depends on the system; the reactions of 7-X gave amides predominantly, whereas 9a-X yielded alcohols as the major product. The logk-logk plots between the systems gave excellent linear correlations with slopes of near unity. The results support the occurrence of path bifurcation after the rate-determining TS of the Beckmann rearrangement/fragmentation reaction, which has previously been proposed on the basis of molecular dynamics simulations. It was concluded that path-bifurcation phenomenon could be more common than thought and that a reactivity-selectivity argument based on the traditional TS theory may not always be applicable even to a well-known textbook organic reaction.

  2. Automated dynamic headspace/GC-MS analyses affect the repeatability of volatiles in irradiated Turkey.

    PubMed

    Nam, Ki-Chang; Cordray, Joseph; Ahn, Dong U

    2004-03-24

    Although a dynamic headspace/gas chromatography-mass spectrometry (DH/GC-MS) method is an effective tool for determining volatiles of irradiated turkey meat, the profile of volatiles may be changeable depending upon the availability of oxygen in the sample vial and sample holding time before purge. The objective of this study was to evaluate the effects of helium flushing and sample holding time before purge on the volatiles profiles of irradiated raw and cooked turkey breast meat. Vacuum-packaged turkey breasts were irradiated at 2.5 kGy, and the volatiles of irradiated raw and cooked samples were analyzed using a DH/GC-MS with different holding times up to 280 min. The amounts of dimethyl disulfide and dimethyl trisulfide decreased as sample holding time in an autosampler (4 degrees C) before purge increased, whereas those of aldehdyes increased as holding time increased due to lipid oxidation. Helium flush of sample vials before sample loading on an autosampler retarded lipid oxidation and minimized the changes of sulfur volatiles in raw meat but was not enough to prevent oxidative changes in cooked meat. Although DH/GC-MS is a convenient method for automatic analysis of volatiles in meat samples, the number of samples that can be loaded in an autosampler at a time should be limited within the range that can permit reasonable repeatabilities for target volatile compounds.

  3. C-Axis Compression of Magnesium Single Crystals: Multi-Scale Dislocation Dynamics Analyses

    NASA Astrophysics Data System (ADS)

    Jaber, Wassim; Shehadeh, Mu'tasem

    Hexagonal-closed packed materials (HCP) materials has attracted interest recently due to their unique physical and mechanical properties. The low density and the high strength to weight ratio of such materials make them excellent candidates to save structural weight and consequently fuel consumption in both automotive and aircraft fields. However, the deformation behavior of HCP metals hasn't been completely understood as prior work still lack a detailed understanding on the activation of slip planes and twinning. In addition, the work-hardening behavior and the effect of temperature and strain rate are not yet well-established. This work aims at investigating the deformation mechanisms in magnesium single crystals using Multiscale Dislocation Dynamics Plasticity (MDDP) model. In particular, we focus on modeling the deformation behavior under c-axis compression loading. Several Simulations have been carried out to study the effect of dislocation mobility dependence on the dislocation character and its consequences on the evolution of the dislocation density, the dislocation microstructure, and the hardening behavior. Preliminary results show that the experimentally observed hardening behavior can be reproduced by using linear interpolation of the mobility such that screw segments are stationary and edge segments are highly mobile.

  4. Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation

    PubMed Central

    Chen, Geng; Schell, John Paul; Benitez, Julio Aguila; Petropoulos, Sophie; Yilmaz, Marlene; Reinius, Björn; Alekseenko, Zhanna; Shi, Leming; Hedlund, Eva; Lanner, Fredrik; Sandberg, Rickard; Deng, Qiaolin

    2016-01-01

    Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI. PMID:27486082

  5. Adaptive coded spreading OFDM signal for dynamic-λ optical access network

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Zhang, Lijia; Xin, Xiangjun

    2015-12-01

    This paper proposes and experimentally demonstrates a novel adaptive coded spreading (ACS) orthogonal frequency division multiplexing (OFDM) signal for dynamic distributed optical ring-based access network. The wavelength can be assigned to different remote nodes (RNs) according to the traffic demand of optical network unit (ONU). The ACS can provide dynamic spreading gain to different signals according to the split ratio or transmission length, which offers flexible power budget for the network. A 10×13.12 Gb/s OFDM access with ACS is successfully demonstrated over two RNs and 120 km transmission in the experiment. The demonstrated method may be viewed as one promising for future optical metro access network.

  6. Subthreshold Dynamics and Its Effect on Signal Transduction in a Neural System

    NASA Astrophysics Data System (ADS)

    Wang, Yuqing; Wang, Z.; Wang, Wei

    1998-10-01

    Subthreshold dynamics and its effect on signal transduction in a neural system are studied by using the Hindmarsh-Rose neuron model. Under a periodic stimulation, as the constant bias of the stimulus increases, the neuron exhibits subthreshold periodic and subthreshold chaotic responses, suprathreshold chaotic firing of spikes, and mode-locked firing. The phase diagram of the system is obtained. The dynamic behavior obtained is in agreement with experiments on the squid giant axon. In particular, the subthreshold periodic oscillatory state is related to a number of experimental results, such as those found in the neurons of the inferior olivary nucleus. More importantly, we also find that subthreshold chaotic responses play a role analogous to the internal deterministic noise, and can enhance weak signal transduction via a mechanism similar to stochastic resonance.

  7. Spacecraft attitude control systems with dynamic methods and structures for processing star tracker signals

    NASA Technical Reports Server (NTRS)

    Liu, Yong (Inventor); Wu, Yeong-Wei Andy (Inventor); Li, Rongsheng (Inventor)

    2001-01-01

    Methods are provided for dynamically processing successively-generated star tracker data frames and associated valid flags to generate processed star tracker signals that have reduced noise and a probability greater than a selected probability P.sub.slctd of being valid. These methods maintain accurate spacecraft attitude control in the presence of spurious inputs (e.g., impinging protons) that corrupt collected charges in spacecraft star trackers. The methods of the invention enhance the probability of generating valid star tracker signals because they respond to a current frame probability P.sub.frm by dynamically selecting the largest valid frame combination whose combination probability P.sub.cmb satisfies a selected probability P.sub.slctd. Noise is thus reduced while the probability of finding a valid frame combination is enhanced. Spacecraft structures are also provided for practicing the methods of the invention.

  8. Adaptive coded spreading OFDM signal for dynamic-λ optical access network

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Zhang, Lijia; Xin, Xiangjun

    2015-12-01

    This paper proposes and experimentally demonstrates a novel adaptive coded spreading (ACS) orthogonal frequency division multiplexing (OFDM) signal for dynamic distributed optical ring-based access network. The wavelength can be assigned to different remote nodes (RNs) according to the traffic demand of optical network unit (ONU). The ACS can provide dynamic spreading gain to different signals according to the split ratio or transmission length, which offers flexible power budget for the network. A 10×13.12 Gb/s OFDM access with ACS is successfully demonstrated over two RNs and 120 km transmission in the experiment. The demonstrated method may be viewed as one promising for future optical metro access network.

  9. Cutting edge: Evidence for a dynamically driven T cell signaling mechanism.

    PubMed

    Hawse, William F; Champion, Matthew M; Joyce, Michelle V; Hellman, Lance M; Hossain, Moushumi; Ryan, Veronica; Pierce, Brian G; Weng, Zhiping; Baker, Brian M

    2012-06-15

    T cells use the αβ TCR to bind peptides presented by MHC proteins (pMHC) on APCs. Formation of a TCR-pMHC complex initiates T cell signaling via a poorly understood process, potentially involving changes in oligomeric state, altered interactions with CD3 subunits, and mechanical stress. These mechanisms could be facilitated by binding-induced changes in the TCR, but the nature and extent of any such alterations are unclear. Using hydrogen/deuterium exchange, we demonstrate that ligation globally rigidifies the TCR, which via entropic and packing effects will promote associations with neighboring proteins and enhance the stability of existing complexes. TCR regions implicated in lateral associations and signaling are particularly affected. Computational modeling demonstrated a high degree of dynamic coupling between the TCR constant and variable domains that is dampened upon ligation. These results raise the possibility that TCR triggering could involve a dynamically driven, allosteric mechanism.

  10. Cell signaling and mitochondrial dynamics: implications for neuronal function and neurodegenerative disease

    PubMed Central

    Wilson, Theodore J.; Slupe, Andrew M.; Strack, Stefan

    2012-01-01

    Nascent evidence indicates that mitochondrial fission, fusion, and transport are subject to intricate regulatory mechanisms that intersect with both well-characterized and emerging signaling pathways. While it is well established that mutations in components of the mitochondrial fission/fusion machinery can cause neurological disorders, relatively little is known about upstream regulators of mitochondrial dynamics and their role in neurodegeneration. Here, we review posttranslational regulation of mitochondrial fission/fusion enzymes, with particular emphasis on dynamin-related protein 1 (Drp1), as well as outer mitochondrial signaling complexes involving protein kinases and phosphatases. We also review recent evidence that mitochondrial dynamics has profound consequences for neuronal development and synaptic transmission and discuss implications for clinical translation. PMID:22297163

  11. Derivation of soil moisture retrieval uncertainties associated to the simplification of the dynamic vegetation signal.

    NASA Astrophysics Data System (ADS)

    Vreugdenhil, Mariette; Dorigo, Wouter; de Jeu, Richard; Hahn, Sebastian; Salinas, Jose Luis; Wagner, Wolfgang

    2014-05-01

    Satellite-based microwave remote sensing has proven to provide reliable soil moisture observations on a global scale over the last decades. In microwave remote sensing of soil moisture the satellite signal holds information on both soil moisture and vegetation. Separating these components from each other is not straightforward. In the last years the importance of a robust and reliable vegetation parameterization within the soil moisture retrieval algorithms has become evident. In the TU-Wien soil moisture retrieval algorithm, developed by the Vienna University of Technology, the backscatter observations are corrected for vegetation effects by way of the slope and curvature. The slope and curvature are derivates of noisy backscatter measurements in relation to incidence angle and hence have a high level of noise. Therefore, they are averaged over several years resulting in a fixed seasonal vegetation correction, where no inter-annual variability is present in the characterisation of vegetation. This study assesses the strengths and weaknesses of the fixed seasonal vegetation correction in the TU-Wien soil moisture retrieval algorithm. The Vegetation Optical Depth (VOD) retrieved from AMSR-E passive microwave observations with the VUA-NASA retrieval algorithm is analysed to identify regions with high inter-annual variability in vegetation. For these regions the effect of a fixed seasonal correction on the soil moisture retrieval is investigated. First, the TU-Wien soil moisture products before and after the application of the vegetation correction, the TU-Wien normalised backscatter and TU-Wien soil moisture respectively, are compared to modelled soil moisture from ECMWFs ERA-Interim. With this analysis regions where the vegetation correction decreases the quality of the TU-Wien soil moisture product with regard to modeled soil moisture can be identified. Secondly, the vegetation correction within the TU-Wien retrieval algorithm is replaced by the VOD to simulate an

  12. Digital signal processing for velocity measurements in dynamical material's behaviour studies.

    PubMed

    Devlaminck, Julien; Luc, Jérôme; Chanal, Pierre-Yves

    2014-03-01

    In this work, we describe different configurations of optical fiber interferometers (types Michelson and Mach-Zehnder) used to measure velocities during dynamical material's behaviour studies. We detail the algorithms of processing developed and optimized to improve the performance of these interferometers especially in terms of time and frequency resolutions. Three methods of analysis of interferometric signals were studied. For Michelson interferometers, the time-frequency analysis of signals by Short-Time Fourier Transform (STFT) is compared to a time-frequency analysis by Continuous Wavelet Transform (CWT). The results have shown that the CWT was more suitable than the STFT for signals with low signal-to-noise, and low velocity and high acceleration areas. For Mach-Zehnder interferometers, the measurement is carried out by analyzing the phase shift between three interferometric signals (Triature processing). These three methods of digital signal processing were evaluated, their measurement uncertainties estimated, and their restrictions or operational limitations specified from experimental results performed on a pulsed power machine.

  13. Digital signal processing for velocity measurements in dynamical material's behaviour studies

    NASA Astrophysics Data System (ADS)

    Devlaminck, Julien; Luc, Jérôme; Chanal, Pierre-Yves

    2014-03-01

    In this work, we describe different configurations of optical fiber interferometers (types Michelson and Mach-Zehnder) used to measure velocities during dynamical material's behaviour studies. We detail the algorithms of processing developed and optimized to improve the performance of these interferometers especially in terms of time and frequency resolutions. Three methods of analysis of interferometric signals were studied. For Michelson interferometers, the time-frequency analysis of signals by Short-Time Fourier Transform (STFT) is compared to a time-frequency analysis by Continuous Wavelet Transform (CWT). The results have shown that the CWT was more suitable than the STFT for signals with low signal-to-noise, and low velocity and high acceleration areas. For Mach-Zehnder interferometers, the measurement is carried out by analyzing the phase shift between three interferometric signals (Triature processing). These three methods of digital signal processing were evaluated, their measurement uncertainties estimated, and their restrictions or operational limitations specified from experimental results performed on a pulsed power machine.

  14. Genetically encoded molecular probes to visualize and perturb signaling dynamics in living biological systems

    PubMed Central

    Sample, Vedangi; Mehta, Sohum; Zhang, Jin

    2014-01-01

    ABSTRACT In this Commentary, we discuss two sets of genetically encoded molecular tools that have significantly enhanced our ability to observe and manipulate complex biochemical processes in their native context and that have been essential in deepening our molecular understanding of how intracellular signaling networks function. In particular, genetically encoded biosensors are widely used to directly visualize signaling events in living cells, and we highlight several examples of basic biosensor designs that have enabled researchers to capture the spatial and temporal dynamics of numerous signaling molecules, including second messengers and signaling enzymes, with remarkable detail. Similarly, we discuss a number of genetically encoded biochemical perturbation techniques that are being used to manipulate the activity of various signaling molecules with far greater spatial and temporal selectivity than can be achieved using standard pharmacological or genetic techniques, focusing specifically on examples of chemically driven and light-inducible perturbation strategies. We then describe recent efforts to combine these diverse and powerful molecular tools into a unified platform that can be used to elucidate the molecular details of biological processes that may potentially extend well beyond the realm of signal transduction. PMID:24634506

  15. An Embedded Statistical Method for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Saether, E.; Glaessgen, E.H.; Yamakov, V.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  16. A New Concurrent Multiscale Methodology for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Yamakov, Vesselin; Saether, Erik; Glaessgen, Edward H/.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  17. Phylogenetic and Metagenomic Analyses of Substrate-Dependent Bacterial Temporal Dynamics in Microbial Fuel Cells

    PubMed Central

    Zhang, Husen; Chen, Xi; Braithwaite, Daniel; He, Zhen

    2014-01-01

    Understanding the microbial community structure and genetic potential of anode biofilms is key to improve extracellular electron transfers in microbial fuel cells. We investigated effect of substrate and temporal dynamics of anodic biofilm communities using phylogenetic and metagenomic approaches in parallel with electrochemical characterizations. The startup non-steady state anodic bacterial structures were compared for a simple substrate, acetate, and for a complex substrate, landfill leachate, using a single-chamber air-cathode microbial fuel cell. Principal coordinate analysis showed that distinct community structures were formed with each substrate type. The bacterial diversity measured as Shannon index decreased with time in acetate cycles, and was restored with the introduction of leachate. The change of diversity was accompanied by an opposite trend in the relative abundance of Geobacter-affiliated phylotypes, which were acclimated to over 40% of total Bacteria at the end of acetate-fed conditions then declined in the leachate cycles. The transition from acetate to leachate caused a decrease in output power density from 243±13 mW/m2 to 140±11 mW/m2, accompanied by a decrease in Coulombic electron recovery from 18±3% to 9±3%. The leachate cycles selected protein-degrading phylotypes within phylum Synergistetes. Metagenomic shotgun sequencing showed that leachate-fed communities had higher cell motility genes including bacterial chemotaxis and flagellar assembly, and increased gene abundance related to metal resistance, antibiotic resistance, and quorum sensing. These differentially represented genes suggested an altered anodic biofilm community in response to additional substrates and stress from the complex landfill leachate. PMID:25202990

  18. A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia

    NASA Astrophysics Data System (ADS)

    Thorwarth, Daniela; Eschmann, Susanne M.; Paulsen, Frank; Alber, Markus

    2005-05-01

    A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.

  19. Hamiltonian model and dynamic analyses for a hydro-turbine governing system with fractional item and time-lag

    NASA Astrophysics Data System (ADS)

    Xu, Beibei; Chen, Diyi; Zhang, Hao; Wang, Feifei; Zhang, Xinguang; Wu, Yonghong

    2017-06-01

    This paper focus on a Hamiltonian mathematical modeling for a hydro-turbine governing system including fractional item and time-lag. With regards to hydraulic pressure servo system, a universal dynamical model is proposed, taking into account the viscoelastic properties and low-temperature impact toughness of constitutive materials as well as the occurrence of time-lag in the signal transmissions. The Hamiltonian model of the hydro-turbine governing system is presented using the method of orthogonal decomposition. Furthermore, a novel Hamiltonian function that provides more detailed energy information is presented, since the choice of the Hamiltonian function is the key issue by putting the whole dynamical system to the theory framework of the generalized Hamiltonian system. From the numerical experiments based on a real large hydropower station, we prove that the Hamiltonian function can describe the energy variation of the hydro-turbine suitably during operation. Moreover, the effect of the fractional α and the time-lag τ on the dynamic variables of the hydro-turbine governing system are explored and their change laws identified, respectively. The physical meaning between fractional calculus and time-lag are also discussed in nature. All of the above theories and numerical results are expected to provide a robust background for the safe operation and control of large hydropower stations.

  20. A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations

    PubMed Central

    Michetti, Davide; Brandsdal, Bjørn Olav; Bon, Davide; Isaksen, Geir Villy; Tiberti, Matteo; Papaleo, Elena

    2017-01-01

    The psychrophilic and mesophilic endonucleases A (EndA) from Aliivibrio salmonicida (VsEndA) and Vibrio cholera (VcEndA) have been studied experimentally in terms of the biophysical properties related to thermal adaptation. The analyses of their static X-ray structures was no sufficient to rationalize the determinants of their adaptive traits at the molecular level. Thus, we used Molecular Dynamics (MD) simulations to compare the two proteins and unveil their structural and dynamical differences. Our simulations did not show a substantial increase in flexibility in the cold-adapted variant on the nanosecond time scale. The only exception is a more rigid C-terminal region in VcEndA, which is ascribable to a cluster of electrostatic interactions and hydrogen bonds, as also supported by MD simulations of the VsEndA mutant variant where the cluster of interactions was introduced. Moreover, we identified three additional amino acidic substitutions through multiple sequence alignment and the analyses of MD-based protein structure networks. In particular, T120V occurs in the proximity of the catalytic residue H80 and alters the interaction with the residue Y43, which belongs to the second coordination sphere of the Mg2+ ion. This makes T120V an amenable candidate for future experimental mutagenesis. PMID:28192428

  1. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1: Preliminary analyses and testing

    NASA Technical Reports Server (NTRS)

    Rhatigan, Jennifer L.; Christiansen, Eric L.; Fleming, Michael L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  2. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1. Preliminary analyses and testing

    SciTech Connect

    Rhatigan, J.L.; Christiansen, E.L.; Fleming, M.L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  3. Dynamic optical interferometry applied to analyse out of plane displacement fields for crack propagation in brittle materials

    NASA Astrophysics Data System (ADS)

    Hedan, S.; Pop, O.; Valle, V.; Cottron, M.

    2006-08-01

    We propose in this paper, to analyse, the evolution of out-of-plane displacement fields for a crack propagation in brittle materials. As the crack propagation is a complex process that involves the deformation mechanisms, the out-of-plane displacement measurement gives pertinent information about the 3D effects. For investigation, we use the interferometric method. The optical device includes a laser source, a Michelson interferometer and an ultra high-speed CCD camera. To take into account the crack velocity, we dispose of a maximum frame rate of 1Mfps. The experimental tests have been carried out for a SEN (Single Edge Notch) specimen of PMMA material. The crack propagation is initiated by adding a dynamic energy given by the impact of a cutter on the initial crack. The obtained interferograms are analysed with a new phase extraction method entitled MPC [6]. This analysis, which has been developed specially for dynamic studies, gives the out-of-plane displacement with an accuracy of about 10 nm.

  4. A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations.

    PubMed

    Michetti, Davide; Brandsdal, Bjørn Olav; Bon, Davide; Isaksen, Geir Villy; Tiberti, Matteo; Papaleo, Elena

    2017-01-01

    The psychrophilic and mesophilic endonucleases A (EndA) from Aliivibrio salmonicida (VsEndA) and Vibrio cholera (VcEndA) have been studied experimentally in terms of the biophysical properties related to thermal adaptation. The analyses of their static X-ray structures was no sufficient to rationalize the determinants of their adaptive traits at the molecular level. Thus, we used Molecular Dynamics (MD) simulations to compare the two proteins and unveil their structural and dynamical differences. Our simulations did not show a substantial increase in flexibility in the cold-adapted variant on the nanosecond time scale. The only exception is a more rigid C-terminal region in VcEndA, which is ascribable to a cluster of electrostatic interactions and hydrogen bonds, as also supported by MD simulations of the VsEndA mutant variant where the cluster of interactions was introduced. Moreover, we identified three additional amino acidic substitutions through multiple sequence alignment and the analyses of MD-based protein structure networks. In particular, T120V occurs in the proximity of the catalytic residue H80 and alters the interaction with the residue Y43, which belongs to the second coordination sphere of the Mg2+ ion. This makes T120V an amenable candidate for future experimental mutagenesis.

  5. Dynamic characteristics of laser Doppler flowmetry signals obtained in response to a local and progressive pressure applied on diabetic and healthy subjects

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Koitka, Audrey; Abraham, Pierre; Saumet, Jean-Louis; L'Huillier, Jean-Pierre

    2004-09-01

    In the biomedical field, the laser Doppler flowmetry (LDF) technique is a non-invasive method to monitor skin perfusion. On the skin of healthy humans, LDF signals present a significant transient increase in response to a local and progressive pressure application. This vasodilatory reflex response may have important implications for cutaneous pathologies involved in various neurological diseases and in the pathophysiology of decubitus ulcers. The present work analyses the dynamic characteristics of these signals on young type 1 diabetic patients, and on healthy age-matched subjects. To obtain accurate dynamic characteristic values, a de-noising wavelet-based algorithm is first applied to LDF signals. All the de-noised signals are then normalised to the same value. The blood flow peak and the time to reach this peak are then calculated on each computed signal. The results show that a large vasodilation is present on signals of healthy subjects. The mean peak occurs at a pressure of 3.2 kPa approximately. However, a vasodilation of limited amplitude appears on type 1 diabetic patients. The maximum value is visualised, on the average, when the pressure is 1.1 kPa. The inability for diabetic patients to increase largely their cutaneous blood flow may bring explanations to foot ulcers.

  6. High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

    PubMed Central

    Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

    2015-01-01

    Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

  7. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    NASA Astrophysics Data System (ADS)

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-12-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems.

  8. Weak temporal signals can synchronize and accelerate the transition dynamics of biopolymers under tension

    PubMed Central

    Kim, Won Kyu; Hyeon, Changbong; Sung, Wokyung

    2012-01-01

    In addition to thermal noise, which is essential to promote conformational transitions in biopolymers, the cellular environment is replete with a spectrum of athermal fluctuations that are produced from a plethora of active processes. To understand the effect of athermal noise on biological processes, we studied how a small oscillatory force affects the thermally induced folding and unfolding transition of an RNA hairpin, whose response to constant tension had been investigated extensively in both theory and experiments. Strikingly, our molecular simulations performed under overdamped condition show that even at a high (low) tension that renders the hairpin (un)folding improbable, a weak external oscillatory force at a certain frequency can synchronously enhance the transition dynamics of RNA hairpin and increase the mean transition rate. Furthermore, the RNA dynamics can still discriminate a signal with resonance frequency even when the signal is mixed among other signals with nonresonant frequencies. In fact, our computational demonstration of thermally induced resonance in RNA hairpin dynamics is a direct realization of the phenomena called stochastic resonance and resonant activation. Our study, amenable to experimental tests using optical tweezers, is of great significance to the folding of biopolymers in vivo that are subject to the broad spectrum of cellular noises. PMID:22908254

  9. Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume

    PubMed Central

    Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

    2016-01-01

    Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions. PMID:27598164

  10. Weak temporal signals can synchronize and accelerate the transition dynamics of biopolymers under tension.

    PubMed

    Kim, Won Kyu; Hyeon, Changbong; Sung, Wokyung

    2012-09-04

    In addition to thermal noise, which is essential to promote conformational transitions in biopolymers, the cellular environment is replete with a spectrum of athermal fluctuations that are produced from a plethora of active processes. To understand the effect of athermal noise on biological processes, we studied how a small oscillatory force affects the thermally induced folding and unfolding transition of an RNA hairpin, whose response to constant tension had been investigated extensively in both theory and experiments. Strikingly, our molecular simulations performed under overdamped condition show that even at a high (low) tension that renders the hairpin (un)folding improbable, a weak external oscillatory force at a certain frequency can synchronously enhance the transition dynamics of RNA hairpin and increase the mean transition rate. Furthermore, the RNA dynamics can still discriminate a signal with resonance frequency even when the signal is mixed among other signals with nonresonant frequencies. In fact, our computational demonstration of thermally induced resonance in RNA hairpin dynamics is a direct realization of the phenomena called stochastic resonance and resonant activation. Our study, amenable to experimental tests using optical tweezers, is of great significance to the folding of biopolymers in vivo that are subject to the broad spectrum of cellular noises.

  11. Digital-signal-processor-based dynamic imaging system for optical tomography.

    PubMed

    Lasker, Joseph M; Masciotti, James M; Schoenecker, Matthew; Schmitz, Christoph H; Hielscher, Andreas H

    2007-08-01

    In this article, we introduce a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. The processor is also responsible for managing system timing and the imaging routines which can acquire real-time data at rates as high as 150 Hz. Many of the synchronously timed processes are controlled by a complex programmable logic device that is also used in conjunction with the DSP to orchestrate data flow. The operation of the system is implemented through a comprehensive graphical user interface designed with LABVIEW software which integrates automated calibration, data acquisition, data organization, and signal postprocessing. Performance analysis demonstrates very low system noise (approximately 1 pW rms noise equivalent power), excellent signal precision (<0.04%-0.2%) and long term system stability (<1% over 40 min). A large dynamic range (approximately 190 dB) accommodates a wide scope of measurement geometries and tissue types. First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system.

  12. Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume.

    PubMed

    Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

    2016-09-02

    Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions.

  13. Exploration of trade-offs between steady-state and dynamic properties in signaling cycles

    NASA Astrophysics Data System (ADS)

    Radivojevic, A.; Chachuat, B.; Bonvin, D.; Hatzimanikatis, V.

    2012-08-01

    In the intracellular signaling networks that regulate important cell processes, the base pattern comprises the cycle of reversible phosphorylation of a protein, catalyzed by kinases and opposing phosphatases. Mathematical modeling and analysis have been used for gaining a better understanding of their functions and to capture the rules governing system behavior. Since biochemical parameters in signaling pathways are not easily accessible experimentally, it is necessary to explore possibilities for both steady-state and dynamic responses in these systems. While a number of studies have focused on analyzing these properties separately, it is necessary to take into account both of these responses simultaneously in order to be able to interpret a broader range of phenotypes. This paper investigates the trade-offs between optimal characteristics of both steady-state and dynamic responses. Following an inverse sensitivity analysis approach, we use systematic optimization methods to find the biochemical and biophysical parameters that simultaneously achieve optimal steady-state and dynamic performance. Remarkably, we find that even a single covalent modification cycle can simultaneously and robustly achieve high ultrasensitivity, high amplification and rapid signal transduction. We also find that the response rise and decay times can be modulated independently by varying the activating- and deactivating-enzyme-to-interconvertible-protein ratios.

  14. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers.

    PubMed

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-12-09

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: "making big noise smaller" by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems.

  15. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    PubMed Central

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-01-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems. PMID:26647650

  16. A Coupled Phase-Temperature Model for Dynamics of Transient Neuronal Signal in Mammals Cold Receptor.

    PubMed

    Kirana, Firman Ahmad; Alatas, Husin; Husein, Irzaman Sulaiman

    2016-01-01

    We propose a theoretical model consisting of coupled differential equation of membrane potential phase and temperature for describing the neuronal signal in mammals cold receptor. Based on the results from previous work by Roper et al., we modified a nonstochastic phase model for cold receptor neuronal signaling dynamics in mammals. We introduce a new set of temperature adjusted functional parameters which allow saturation characteristic at high and low steady temperatures. The modified model also accommodates the transient neuronal signaling process from high to low temperature by introducing a nonlinear differential equation for the "effective temperature" changes which is coupled to the phase differential equation. This simple model can be considered as a candidate for describing qualitatively the physical mechanism of the corresponding transient process.

  17. Dynamic lightpath provisioning with signal quality guarantees in survivable translucent optical networks.

    PubMed

    Ouyang, Yong; Zeng, Qingji; Wei, Wei

    2005-12-26

    This paper studies the problem of signal-quality-guaranteed lightpath provisioning in survivable translucent optical networks under dynamic traffic. A new protection scheme, called regeneration-segment protection (RSP), is proposed. Provisioning approaches with shared path protection and shared RSP are presented. Two main signal quality constraints are integrated with the provisioning problem. Different regenerator placement strategies for working path and protection path are employed. Joint path selection method is used to select the "optimal" working-protection pair. With the above considerations, survivable lightpath provisioning with signal-quality-guarantees is achieved in a cost-effective manner. Results show that in a moderate-size network, RSP has less blocking probability than path protection when the network load is low or modest. Besides, RSP obtains better performance in terms of recovery time than path protection in all network scenarios.

  18. Label-Free Imaging of Dynamic and Transient Calcium Signaling in Single Cells.

    PubMed

    Lu, Jin; Li, Jinghong

    2015-11-09

    Cell signaling consists of diverse events that occur at various temporal and spatial scales, ranging from milliseconds to hours and from single biomolecules to cell populations. The pathway complexities require the development of new techniques that detect the overall signaling activities and are not limited to quantifying a single event. A plasmonic-based electrochemical impedance microscope (P-EIM) that can provide such data with excellent temporal and spatial resolution and does not require the addition of any labels for detection has now been developed. The highly dynamic and transient calcium signaling activities at the early stage of G-protein-coupled receptor (GPCR) stimulation were thus studied. It could be shown that a subpopulation of cells is more responsive towards agonist stimulation, and the heterogeneity of the local distributions and the transient activities of the ion channels during agonist-activated calcium flux in single HeLa cells were investigated.

  19. A mesoscale abscisic acid hormone interactome reveals a dynamic signaling landscape in Arabidopsis.

    PubMed

    Lumba, Shelley; Toh, Shigeo; Handfield, Louis-François; Swan, Michael; Liu, Raymond; Youn, Ji-Young; Cutler, Sean R; Subramaniam, Rajagopal; Provart, Nicholas; Moses, Alan; Desveaux, Darrell; McCourt, Peter

    2014-05-12

    The sesquiterpenoid abscisic acid (ABA) mediates an assortment of responses across a variety of kingdoms including both higher plants and animals. In plants, where most is known, a linear core ABA signaling pathway has been identified. However, the complexity of ABA-dependent gene expression suggests that ABA functions through an intricate network. Here, using systems biology approaches that focused on genes transcriptionally regulated by ABA, we defined an ABA signaling network of over 500 interactions among 138 proteins. This map greatly expanded ABA core signaling but was still manageable for systematic analysis. For example, functional analysis was used to identify an ABA module centered on two sucrose nonfermenting (SNF)-like kinases. We also used coexpression analysis of interacting partners within the network to uncover dynamic subnetwork structures in response to different abiotic stresses. This comprehensive ABA resource allows for application of approaches to understanding ABA functions in higher plants. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. A Coupled Phase-Temperature Model for Dynamics of Transient Neuronal Signal in Mammals Cold Receptor

    PubMed Central

    Kirana, Firman Ahmad; Husein, Irzaman Sulaiman

    2016-01-01

    We propose a theoretical model consisting of coupled differential equation of membrane potential phase and temperature for describing the neuronal signal in mammals cold receptor. Based on the results from previous work by Roper et al., we modified a nonstochastic phase model for cold receptor neuronal signaling dynamics in mammals. We introduce a new set of temperature adjusted functional parameters which allow saturation characteristic at high and low steady temperatures. The modified model also accommodates the transient neuronal signaling process from high to low temperature by introducing a nonlinear differential equation for the “effective temperature” changes which is coupled to the phase differential equation. This simple model can be considered as a candidate for describing qualitatively the physical mechanism of the corresponding transient process. PMID:27774102

  1. Cellular context–mediated Akt dynamics regulates MAP kinase signaling thresholds during angiogenesis

    PubMed Central

    Hellesøy, Monica; Lorens, James B.

    2015-01-01

    The formation of new blood vessels by sprouting angiogenesis is tightly regulated by contextual cues that affect angiogeneic growth factor signaling. Both constitutive activation and loss of Akt kinase activity in endothelial cells impair angiogenesis, suggesting that Akt dynamics mediates contextual microenvironmental regulation. We explored the temporal regulation of Akt in endothelial cells during formation of capillary-like networks induced by cell–cell contact with vascular smooth muscle cells (vSMCs) and vSMC-associated VEGF. Expression of constitutively active Akt1 strongly inhibited network formation, whereas hemiphosphorylated Akt1 epi-alleles with reduced kinase activity had an intermediate inhibitory effect. Conversely, inhibition of Akt signaling did not affect endothelial cell migration or morphogenesis in vSMC cocultures that generate capillary-like structures. We found that endothelial Akt activity is transiently blocked by proteasomal degradation in the presence of SMCs during the initial phase of capillary-like structure formation. Suppressed Akt activity corresponded to the increased endothelial MAP kinase signaling that was required for angiogenic endothelial morphogenesis. These results reveal a regulatory principle by which cellular context regulates Akt protein dynamics, which determines MAP kinase signaling thresholds necessary drive a morphogenetic program during angiogenesis. PMID:26023089

  2. Dynamic pathway modeling of signal transduction networks: a domain-oriented approach.

    PubMed

    Conzelmann, Holger; Gilles, Ernst-Dieter

    2008-01-01

    Mathematical models of biological processes become more and more important in biology. The aim is a holistic understanding of how processes such as cellular communication, cell division, regulation, homeostasis, or adaptation work, how they are regulated, and how they react to perturbations. The great complexity of most of these processes necessitates the generation of mathematical models in order to address these questions. In this chapter we provide an introduction to basic principles of dynamic modeling and highlight both problems and chances of dynamic modeling in biology. The main focus will be on modeling of s transduction pathways, which requires the application of a special modeling approach. A common pattern, especially in eukaryotic signaling systems, is the formation of multi protein signaling complexes. Even for a small number of interacting proteins the number of distinguishable molecular species can be extremely high. This combinatorial complexity is due to the great number of distinct binding domains of many receptors and scaffold proteins involved in signal transduction. However, these problems can be overcome using a new domain-oriented modeling approach, which makes it possible to handle complex and branched signaling pathways.

  3. Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

    PubMed

    Gast, Heidemarie; Müller, Markus; Rummel, Christian; Roth, Corinne; Mathis, Johannes; Schindler, Kaspar; Bassetti, Claudio L

    2014-06-01

    Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures.

  4. Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

    PubMed Central

    Wakayama, Tadashi; Suzuki, Masaaki; Tanuma, Tadashi

    2016-01-01

    Objective Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. Methods We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. Results Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. Conclusion This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow

  5. Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses.

    PubMed

    Wakayama, Tadashi; Suzuki, Masaaki; Tanuma, Tadashi

    2016-01-01

    Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject's CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow velocity was found.

  6. Daniel K. Inouye Solar Telescope: computational fluid dynamic analyses and evaluation of the air knife model

    NASA Astrophysics Data System (ADS)

    McQuillen, Isaac; Phelps, LeEllen; Warner, Mark; Hubbard, Robert

    2016-08-01

    Implementation of an air curtain at the thermal boundary between conditioned and ambient spaces allows for observation over wavelength ranges not practical when using optical glass as a window. The air knife model of the Daniel K. Inouye Solar Telescope (DKIST) project, a 4-meter solar observatory that will be built on Haleakalā, Hawai'i, deploys such an air curtain while also supplying ventilation through the ceiling of the coudé laboratory. The findings of computational fluid dynamics (CFD) analysis and subsequent changes to the air knife model are presented. Major design constraints include adherence to the Interface Control Document (ICD), separation of ambient and conditioned air, unidirectional outflow into the coudé laboratory, integration of a deployable glass window, and maintenance and accessibility requirements. Optimized design of the air knife successfully holds full 12 Pa backpressure under temperature gradients of up to 20°C while maintaining unidirectional outflow. This is a significant improvement upon the .25 Pa pressure differential that the initial configuration, tested by Linden and Phelps, indicated the curtain could hold. CFD post- processing, developed by Vogiatzis, is validated against interferometry results of initial air knife seeing evaluation, performed by Hubbard and Schoening. This is done by developing a CFD simulation of the initial experiment and using Vogiatzis' method to calculate error introduced along the optical path. Seeing error, for both temperature differentials tested in the initial experiment, match well with seeing results obtained from the CFD analysis and thus validate the post-processing model. Application of this model to the realizable air knife assembly yields seeing errors that are well within the error budget under which the air knife interface falls, even with a temperature differential of 20°C between laboratory and ambient spaces. With ambient temperature set to 0°C and conditioned temperature set to 20

  7. Extracting a respiratory signal from raw dynamic PET data that contain tracer kinetics

    NASA Astrophysics Data System (ADS)

    Schleyer, P. J.; Thielemans, K.; Marsden, P. K.

    2014-08-01

    Data driven gating (DDG) methods provide an alternative to hardware based respiratory gating for PET imaging. Several existing DDG approaches obtain a respiratory signal by observing the change in PET-counts within specific regions of acquired PET data. Currently, these methods do not allow for tracer kinetics which can interfere with the respiratory signal and introduce error. In this work, we produced a DDG method for dynamic PET studies that exhibit tracer kinetics. Our method is based on an existing approach that uses frequency-domain analysis to locate regions within raw PET data that are subject to respiratory motion. In the new approach, an optimised non-stationary short-time Fourier transform was used to create a time-varying 4D map of motion affected regions. Additional processing was required to ensure that the relationship between the sign of the respiratory signal and the physical direction of movement remained consistent for each temporal segment of the 4D map. The change in PET-counts within the 4D map during the PET acquisition was then used to generate a respiratory curve. Using 26 min dynamic cardiac NH3 PET acquisitions which included a hardware derived respiratory measurement, we show that tracer kinetics can severely degrade the respiratory signal generated by the original DDG method. In some cases, the transition of tracer from the liver to the lungs caused the respiratory signal to invert. The new approach successfully compensated for tracer kinetics and improved the correlation between the data-driven and hardware based signals. On average, good correlation was maintained throughout the PET acquisitions.

  8. Automated region of interest analysis of dynamic Ca2+ signals in image sequences

    PubMed Central

    Francis, Michael; Qian, Xun; Charbel, Chimène; Ledoux, Jonathan; Parker, J. C.

    2012-01-01

    Ca2+ signals are commonly measured using fluorescent Ca2+ indicators and microscopy techniques, but manual analysis of Ca2+ measurements is time consuming and subject to bias. Automated region of interest (ROI) detection algorithms have been employed for identification of Ca2+ signals in one-dimensional line scan images, but currently there is no process to integrate acquisition and analysis of ROIs within two-dimensional time lapse image sequences. Therefore we devised a novel algorithm for rapid ROI identification and measurement based on the analysis of best-fit ellipses assigned to signals within noise-filtered image sequences. This algorithm was implemented as a plugin for ImageJ software (National Institutes of Health, Bethesda, MD). We evaluated the ability of our algorithm to detect synthetic Gaussian signal pulses embedded in background noise. The algorithm placed ROIs very near to the center of a range of signal pulses, resulting in mean signal amplitude measurements of 99.06 ± 4.11% of true amplitude values. As a practical application, we evaluated both agonist-induced Ca2+ responses in cultured endothelial cell monolayers, and subtle basal endothelial Ca2+ dynamics in opened artery preparations. Our algorithm enabled comprehensive measurement of individual and localized cellular responses within cultured cell monolayers. It also accurately identified characteristic Ca2+ transients, or Ca2+ pulsars, within the endothelium of intact mouse mesenteric arteries and revealed the distribution of this basal Ca2+ signal modality to be non-Gaussian with respect to amplitude, duration, and spatial spread. We propose that large-scale statistical evaluations made possible by our algorithm will lead to a more efficient and complete characterization of physiologic Ca2+-dependent signaling. PMID:22538238

  9. Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway.

    PubMed

    Liu, Lin; Channavajhala, Padma L; Rao, Vikram R; Moutsatsos, Ioannis; Wu, Leeying; Zhang, Yuhua; Lin, Lih-Ling; Qiu, Yongchang

    2009-10-01

    KSR-1 is a scaffold protein that is essential for Ras-induced activation of the highly conserved RAF-MEK-ERK kinase module. Previously, we identified a close homolog of KSR-1, called KSR-2, through structural homology-based data mining. In order to further understand the role of KSR-2 in MAPK signaling, we undertook a functional proteomics approach to elucidate the dynamic composition of the KSR-2 functional complex in HEK-293 cells under conditions with and without TNF-alpha stimulation. We found nearly 100 proteins that were potentially associated with KSR-2 complex and 43 proteins that were likely recruited to the super molecular complex after TNF-alpha treatment. Our results indicate that KSR-2 may act as a scaffold protein similar as KSR-1 to mediate the MAPK core (RAF-MEK-ERK) signaling but with a distinct RAF isoform specificity, namely KSR-2 may only mediate the A-RAF signaling while KSR-1 is responsible for transducing signals only from c-RAF. In addition, KSR-2 may be involved in the activation of many MAPK downstream signaling molecules such as p38 MAPK, IKAP, AIF, and proteins involved in ubiquitin-proteasome, apoptosis, cell cycle control, and DNA synthesis and repair pathways, as well as mediating crosstalks between MAPK and several other signaling pathways, including PI3K and insulin signaling. While interactions with these molecules are not known for KSR-1, it's reasonable to hypothesize that KSR-1 may also play a similar role in mediating these downstream signaling pathways.

  10. Novel optical-based methods and analyses for elucidating cellular mechanics and dynamics

    NASA Astrophysics Data System (ADS)

    Koo, Peter K.

    Resolving distinct biochemical interaction states by analyzing the diffusive behaviors of individual protein trajectories is challenging due to the limited statistics provided by short trajectories and experimental noise sources, which are intimately coupled into each proteins localization. In the first part of this thesis, we introduce a novel, a machine-learning based classification methodology, called perturbation expectation-maximization (pEM), which simultaneously analyzes a population of protein trajectories to uncover the system of short-time diffusive behaviors which collectively result from distinct biochemical interactions. We then discuss an experimental application of pEM to Rho GTPase, an integral regulator of cytoskeletal dynamics and cellular homeostasis, inside live cells. We also derive the maximum likelihood estimator (MLE) for driven diffusion, confined diffusion, and fractional Brownian motion. We demonstrate that MLE yields improved estimates in comparison with traditional diffusion analysis, namely mean squared displacement analysis. In addition, we also introduce mleBayes, which is an empirical Bayesian model selection scheme to classify an individual protein trajectory to a given diffusion mode. By employing mleBayes on simulated data, we demonstrate that accurate determination of the underlying diffusive properties, beyond normal diffusion, remains challenging when analyzing particle trajectories on an individual basis. To improve upon the statistical limitations of classification from analyzing trajectories on an individual basis, we extend pEM with a new version (pEMv2) to simultaneously analyzing a collection of particle trajectories to uncover the system of interactions which give rise to unique normal or non-normal diffusive states. We test the performance of pEMv2 on various sets of simulated particle trajectories which transition between various modes of normal and non-normal diffusive states to highlight considerations when

  11. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  12. Detection of a dynamic topography signal in last interglacial sea-level records

    PubMed Central

    Austermann, Jacqueline; Mitrovica, Jerry X.; Huybers, Peter; Rovere, Alessio

    2017-01-01

    Estimating minimum ice volume during the last interglacial based on local sea-level indicators requires that these indicators are corrected for processes that alter local sea level relative to the global average. Although glacial isostatic adjustment is generally accounted for, global scale dynamic changes in topography driven by convective mantle flow are generally not considered. We use numerical models of mantle flow to quantify vertical deflections caused by dynamic topography and compare predictions at passive margins to a globally distributed set of last interglacial sea-level markers. The deflections predicted as a result of dynamic topography are significantly correlated with marker elevations (>95% probability) and are consistent with construction and preservation attributes across marker types. We conclude that a dynamic topography signal is present in the elevation of last interglacial sea-level records and that the signal must be accounted for in any effort to determine peak global mean sea level during the last interglacial to within an accuracy of several meters. PMID:28695210

  13. Detection of a dynamic topography signal in last interglacial sea-level records.

    PubMed

    Austermann, Jacqueline; Mitrovica, Jerry X; Huybers, Peter; Rovere, Alessio

    2017-07-01

    Estimating minimum ice volume during the last interglacial based on local sea-level indicators requires that these indicators are corrected for processes that alter local sea level relative to the global average. Although glacial isostatic adjustment is generally accounted for, global scale dynamic changes in topography driven by convective mantle flow are generally not considered. We use numerical models of mantle flow to quantify vertical deflections caused by dynamic topography and compare predictions at passive margins to a globally distributed set of last interglacial sea-level markers. The deflections predicted as a result of dynamic topography are significantly correlated with marker elevations (>95% probability) and are consistent with construction and preservation attributes across marker types. We conclude that a dynamic topography signal is present in the elevation of last interglacial sea-level records and that the signal must be accounted for in any effort to determine peak global mean sea level during the last interglacial to within an accuracy of several meters.

  14. Human-arm-and-hand-dynamic model with variability analyses for a stylus-based haptic interface.

    PubMed

    Fu, Michael J; Cavuşoğlu, M Cenk

    2012-12-01

    Haptic interface research benefits from accurate human arm models for control and system design. The literature contains many human arm dynamic models but lacks detailed variability analyses. Without accurate measurements, variability is modeled in a very conservative manner, leading to less than optimal controller and system designs. This paper not only presents models for human arm dynamics but also develops inter- and intrasubject variability models for a stylus-based haptic device. Data from 15 human subjects (nine male, six female, ages 20-32) were collected using a Phantom Premium 1.5a haptic device for system identification. In this paper, grip-force-dependent models were identified for 1-3-N grip forces in the three spatial axes. Also, variability due to human subjects and grip-force variation were modeled as both structured and unstructured uncertainties. For both forms of variability, the maximum variation, 95 %, and 67 % confidence interval limits were examined. All models were in the frequency domain with force as input and position as output. The identified models enable precise controllers targeted to a subset of possible human operator dynamics.

  15. Individual-Environment Interactions in Swimming: The Smallest Unit for Analysing the Emergence of Coordination Dynamics in Performance?

    PubMed

    Guignard, Brice; Rouard, Annie; Chollet, Didier; Hart, John; Davids, Keith; Seifert, Ludovic

    2017-02-08

    Displacement in competitive swimming is highly dependent on fluid characteristics, since athletes use these properties to propel themselves. It is essential for sport scientists and practitioners to clearly identify the interactions that emerge between each individual swimmer and properties of an aquatic environment. Traditionally, the two protagonists in these interactions have been studied separately. Determining the impact of each swimmer's movements on fluid flow, and vice versa, is a major challenge. Classic biomechanical research approaches have focused on swimmers' actions, decomposing stroke characteristics for analysis, without exploring perturbations to fluid flows. Conversely, fluid mechanics research has sought to record fluid behaviours, isolated from the constraints of competitive swimming environments (e.g. analyses in two-dimensions, fluid flows passively studied on mannequins or robot effectors). With improvements in technology, however, recent investigations have focused on the emergent circular couplings between swimmers' movements and fluid dynamics. Here, we provide insights into concepts and tools that can explain these on-going dynamic interactions in competitive swimming within the theoretical framework of ecological dynamics.

  16. Transcriptomic network analyses of leaf dehydration responses identify highly connected ABA and ethylene signaling hubs in three grapevine species differing in drought tolerance.

    PubMed

    Hopper, Daniel W; Ghan, Ryan; Schlauch, Karen A; Cramer, Grant R

    2016-05-23

    Grapevine is a major food crop that is affected by global climate change. Consistent with field studies, dehydration assays of grapevine leaves can reveal valuable information of the plant's response at physiological, transcript, and protein levels. There are well-known differences in grapevine rootstocks responses to dehydration. We used time-series transcriptomic approaches combined with network analyses to elucidate and identify important physiological processes and network hubs that responded to dehydration in three different grapevine species differing in their drought tolerance. Transcriptomic analyses of the leaves of Cabernet Sauvignon, Riparia Gloire, and Ramsey were evaluated at different times during a 24-h controlled dehydration. Analysis of variance (ANOVA) revealed that approximately 11,000 transcripts changed significantly with respect to the genotype x treatment interaction term and approximately 6000 transcripts changed significantly according to the genotype x treatment x time interaction term indicating massive differential changes in gene expression over time. Standard analyses determined substantial effects on the transcript abundance of genes involved in the metabolism and signaling of two known plant stress hormones, abscisic acid (ABA) and ethylene. ABA and ethylene signaling maps were constructed and revealed specific changes in transcript abundance that were associated with the known drought tolerance of the genotypes including genes such as VviABI5, VviABF2, VviACS2, and VviWRKY22. Weighted-gene coexpression network analysis (WGCNA) confirmed these results. In particular, WGCNA identified 30 different modules, some of which had highly enriched gene ontology (GO) categories for photosynthesis, phenylpropanoid metabolism, ABA and ethylene signaling. The ABA signaling transcription factors, VviABI5 and VviABF2, were highly connected hubs in two modules, one being enriched in gaseous transport and the other in ethylene signaling. VviABI5 was

  17. A digital-signal-processor-based optical tomographic system for dynamic imaging of joint diseases

    NASA Astrophysics Data System (ADS)

    Lasker, Joseph M.

    Over the last decade, optical tomography (OT) has emerged as viable biomedical imaging modality. Various imaging systems have been developed that are employed in preclinical as well as clinical studies, mostly targeting breast imaging, brain imaging, and cancer related studies. Of particular interest are so-called dynamic imaging studies where one attempts to image changes in optical properties and/or physiological parameters as they occur during a system perturbation. To successfully perform dynamic imaging studies, great effort is put towards system development that offers increasingly enhanced signal-to-noise performance at ever shorter data acquisition times, thus capturing high fidelity tomographic data within narrower time periods. Towards this goal, I have developed in this thesis a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this instrument is a digital signal processor (DSP) that collects, collates, and processes the digitized data set. Complementary protocols between the DSP and a complex programmable logic device synchronizes the sampling process and organizes data flow. Instrument control is implemented through a comprehensive graphical user interface which integrates automated calibration, data acquisition, and signal post-processing. Real-time data is generated at frame rates as high as 140 Hz. An extensive dynamic range (˜190 dB) accommodates a wide scope of measurement geometries and tissue types. Performance analysis demonstrates very low system noise (˜1 pW rms noise equivalent power), excellent signal precision (˜0.04%--0.2%) and long term system stability (˜1% over 40 min). Experiments on tissue phantoms validate spatial and temporal accuracy of the system. As a potential new application of dynamic optical imaging I present the first application of this method to use vascular hemodynamics as a means of characterizing

  18. A parallel unbalanced digitization architecture to reduce the dynamic range of multiple signals

    NASA Astrophysics Data System (ADS)

    Vallérian, Mathieu; HuÅ£u, Florin; Villemaud, Guillaume; Miscopein, Benoît; Risset, Tanguy

    2016-05-01

    Technologies employed in urban sensor networks are permanently evolving, and thus the gateways employed to collect data in such kind of networks have to be very flexible in order to be compliant with the new communication standards. A convenient way to do that is to digitize all the received signals in one shot and then to digitally perform the signal processing, as it is done in software-defined radio (SDR). All signals can be emitted with very different features (bandwidth, modulation type, and power level) in order to respond to the various propagation conditions. Their difference in terms of power levels is a problem when digitizing them together, as no current commercial analog-to-digital converter (ADC) can provide a fine enough resolution to digitize this high dynamic range between the weakest possible signal in the presence of a stronger signal. This paper presents an RF front end receiver architecture capable of handling this problem by using two ADCs of lower resolutions. The architecture is validated through a set of simulations using Keysight's ADS software. The main validation criterion is the bit error rate comparison with a classical receiver.

  19. A robust color signal processing with wide dynamic range WRGB CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Kawada, Shun; Kuroda, Rihito; Sugawa, Shigetoshi

    2011-01-01

    We have developed a robust color reproduction methodology by a simple calculation with a new color matrix using the formerly developed wide dynamic range WRGB lateral overflow integration capacitor (LOFIC) CMOS image sensor. The image sensor was fabricated through a 0.18 μm CMOS technology and has a 45 degrees oblique pixel array, the 4.2 μm effective pixel pitch and the W pixels. A W pixel was formed by replacing one of the two G pixels in the Bayer RGB color filter. The W pixel has a high sensitivity through the visible light waveband. An emerald green and yellow (EGY) signal is generated from the difference between the W signal and the sum of RGB signals. This EGY signal mainly includes emerald green and yellow lights. These colors are difficult to be reproduced accurately by the conventional simple linear matrix because their wave lengths are in the valleys of the spectral sensitivity characteristics of the RGB pixels. A new linear matrix based on the EGY-RGB signal was developed. Using this simple matrix, a highly accurate color processing with a large margin to the sensitivity fluctuation and noise has been achieved.

  20. Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

    PubMed Central

    Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

    2016-01-01

    Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

  1. The relation of signal transduction to the sensitivity and dynamic range of bacterial chemotaxis.

    PubMed

    Namba, Toshinori; Nishikawa, Masatoshi; Shibata, Tatsuo

    2012-09-19

    Complex networks of interacting molecular components of living cells are responsible for many important processes, such as signal processing and transduction. An important challenge is to understand how the individual properties of these molecular interactions and biochemical transformations determine the system-level properties of biological functions. Here, we address the issue of the accuracy of signal transduction performed by a bacterial chemotaxis system. The chemotaxis sensitivity of bacteria to a chemoattractant gradient has been measured experimentally from bacterial aggregation in a chemoattractant-containing capillary. The observed precision of the chemotaxis depended on environmental conditions such as the concentration and molecular makeup of the chemoattractant. In a quantitative model, we derived the chemotactic response function, which is essential to describing the signal transduction process involved in bacterial chemotaxis. In the presence of a gradient, an analytical solution is derived that reveals connections between the chemotaxis sensitivity and the characteristics of the signaling system, such as reaction rates. These biochemical parameters are integrated into two system-level parameters: one characterizes the efficiency of gradient sensing, and the other is related to the dynamic range of chemotaxis. Thus, our approach explains how a particular signal transduction property affects the system-level performance of bacterial chemotaxis. We further show that the two parameters can be derived from published experimental data from a capillary assay, which successfully characterizes the performance of bacterial chemotaxis.

  2. S-EMG signal compression based on domain transformation and spectral shape dynamic bit allocation

    PubMed Central

    2014-01-01

    Background Surface electromyographic (S-EMG) signal processing has been emerging in the past few years due to its non-invasive assessment of muscle function and structure and because of the fast growing rate of digital technology which brings about new solutions and applications. Factors such as sampling rate, quantization word length, number of channels and experiment duration can lead to a potentially large volume of data. Efficient transmission and/or storage of S-EMG signals are actually a research issue. That is the aim of this work. Methods This paper presents an algorithm for the data compression of surface electromyographic (S-EMG) signals recorded during isometric contractions protocol and during dynamic experimental protocols such as the cycling activity. The proposed algorithm is based on discrete wavelet transform to proceed spectral decomposition and de-correlation, on a dynamic bit allocation procedure to code the wavelets transformed coefficients, and on an entropy coding to minimize the remaining redundancy and to pack all data. The bit allocation scheme is based on mathematical decreasing spectral shape models, which indicates a shorter digital word length to code high frequency wavelets transformed coefficients. Four bit allocation spectral shape methods were implemented and compared: decreasing exponential spectral shape, decreasing linear spectral shape, decreasing square-root spectral shape and rotated hyperbolic tangent spectral shape. Results The proposed method is demonstrated and evaluated for an isometric protocol and for a dynamic protocol using a real S-EMG signal data bank. Objective performance evaluations metrics are presented. In addition, comparisons with other encoders proposed in scientific literature are shown. Conclusions The decreasing bit allocation shape applied to the quantized wavelet coefficients combined with arithmetic coding results is an efficient procedure. The performance comparisons of the proposed S-EMG data

  3. Fluid dynamics alter Caenorhabditis elegans body length via TGF-β/DBL-1 neuromuscular signaling

    PubMed Central

    Harada, Shunsuke; Hashizume, Toko; Nemoto, Kanako; Shao, Zhenhua; Higashitani, Nahoko; Etheridge, Timothy; Szewczyk, Nathaniel J; Fukui, Keiji; Higashibata, Akira; Higashitani, Atsushi

    2016-01-01

    Skeletal muscle wasting is a major obstacle for long-term space exploration. Similar to astronauts, the nematode Caenorhabditis elegans displays negative muscular and physical effects when in microgravity in space. It remains unclear what signaling molecules and behavior(s) cause these negative alterations. Here we studied key signaling molecules involved in alterations of C. elegans physique in response to fluid dynamics in ground-based experiments. Placing worms in space on a 1G accelerator increased a myosin heavy chain, myo-3, and a transforming growth factor-β (TGF-β), dbl-1, gene expression. These changes also occurred when the fluid dynamic parameters viscosity/drag resistance or depth of liquid culture were increased on the ground. In addition, body length increased in wild type and body wall cuticle collagen mutants, rol-6 and dpy-5, grown in liquid culture. In contrast, body length did not increase in TGF-β, dbl-1, or downstream signaling pathway, sma-4/Smad, mutants. Similarly, a D1-like dopamine receptor, DOP-4, and a mechanosensory channel, UNC-8, were required for increased dbl-1 expression and altered physique in liquid culture. As C. elegans contraction rates are much higher when swimming in liquid than when crawling on an agar surface, we also examined the relationship between body length enhancement and rate of contraction. Mutants with significantly reduced contraction rates were typically smaller. However, in dop-4, dbl-1, and sma-4 mutants, contraction rates still increased in liquid. These results suggest that neuromuscular signaling via TGF-β/DBL-1 acts to alter body physique in response to environmental conditions including fluid dynamics. PMID:28725724

  4. Evaluating dynamic global vegetation models using meta-data analyses on soil carbon changes following land use change

    NASA Astrophysics Data System (ADS)

    Nyawira, Sylvia; Don, Axel; Nabel, Julia; Brovkin, Victor; Pongratz, Julia

    2015-04-01

    A major driver of changes in soil carbon in recent centuries has been land-use change. While evidence of land-use-related soil carbon changes exists based on local-scale observations, global estimates of these changes rely on modeling and remain highly uncertain. To understand the applicability of models to making future projections of soil carbon changes due to land use change, it is important to evaluate models using observations on soil carbon. A range of meta-data analyses on soil carbon changes following land use change has been published recently, aggregating local observations to levels potentially applicable to dynamic global vegetation models (DGVMs). However, up to now, this data has not been compared to DGVM simulations. The aim of this work is to develop an approach for evaluating DGVMs using these meta-analyses and apply the approach to evaluate the newly implemented soil carbon scheme-YASSO in the DGVM-JSBACH. YASSO is driven by vegetation productivity from JSBACH. However, the productivity by JSBACH is known to have biases in some regions as compared to what is observed in reality. To account for these biases, we confine the litter inputs to soils close to observations and constrain the decomposition by forcing YASSO with observed vegetation productivity and climate. Later we assess the bias introduced by JSBACH vegetation productivity on the soil carbon response in YASSO. We perform idealized simulations from one land-use to another to mimic the observational set-ups that the meta-data analyses comprise. To compare the simulated soil carbon response in the model with the meta-data, we select homogeneous physical regions based on the factors identified in literature as to influence the spatial and temporal variability of changes in soil carbon following land use change. Both the simulated equilibrium and the transient response of soil carbon to land use change simulated by YASSO for these regions is then compared with the meta-data analyses.

  5. Flow dynamics of stenotic aortic valves assessed by signal processing of Doppler spectrograms.

    PubMed

    Bermejo, J; Antoranz, J C; García-Fernández, M A; Moreno, M M; Delcán, J L

    2000-03-01

    Clinical assessment of aortic stenosis (AS) is sometimes challenging, because all hemodynamic indexes of severity are modified by flow rate. However, the mechanisms underlying flow dependence remain controversial. Analysis of instantaneous flow dynamics has provided crucial information in a number of cardiovascular disorders and may add new insight into this phenomenon. This study was designed to analyze in vivo the effects of flow interventions on instantaneous valvular dynamics of stenotic valves. For this purpose, a custom algorithm for signal processing of Doppler spectrograms was developed and validated against a control population. Digital Doppler recordings at the aortic valve and left ventricular outflow tract were obtained in 15 patients with AS, at baseline and during low-dose dobutamine infusion; 10 normal subjects were studied as controls. Spectrograms were processed by signal averaging, time alignment, modal-velocity enhancement, envelope tracing, and numerical interpolation. Instantaneous relative aortic valve area (rAVA) was obtained by the continuity equation and plotted against normalized ejection time. Curves were classified as either type A (rapid, early-systolic opening) or type B (slow, end-systolic opening). Curves from controls closely matched prior knowledge of normal valve dynamics, but curves from patients were clearly different: all controls except 2 (80%) had type A, whereas all patients except 3 (80%) had a type B pattern (p = 0.03). Dobutamine infusion in patients increased and slightly anticipated peak rAVA by accelerating valve opening. Despite similar values of area and pressure difference, type B dynamics were associated with lower blood pressure (p = 0.01) and worse long-term outcome (>3 years) than type A flow dynamics (p = 0.02). Signal processing of Doppler spectrograms allows a comprehensive assessment of aortic flow dynamics. Differences in timing of valve aperture and in maximal leaflet excursion account for flow

  6. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling

    PubMed Central

    Wen, Ya; Alshikho, Mohamad J.; Herbert, Martha R.

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging—they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)—and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process “calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK” is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic

  7. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

    PubMed Central

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388

  8. Detection of a dynamic topography signal in last interglacial sea level records

    NASA Astrophysics Data System (ADS)

    Austermann, Jacqueline; Mitrovica, Jerry X.; Huybers, Peter; Rovere, Alessio

    2017-04-01

    Mantle convection driven changes in topography have been shown to warp Earth's surface on long (million year) timescales, causing flooding and widespread sea level change. We argue that changes in dynamic topography also play a role in sea level changes on the shorter timescale of glacial cycles. The Last Interglacial (LIG, 125 ka) serves as a testing ground for understanding ice sheet stability and sea level rise in a warmer world. Global mean sea level during this time is generally obtained by correcting the observed elevation of sea level indicators for glacial isostatic adjustment. Here we investigate the extent to which mantle convection has additionally impacted the elevation of interglacial sea level markers. We consider the full effect of mantle flow driven changes in topography, including the thermal subsidence of ocean lithosphere and conduct twelve mantle convection calculations to estimate the magnitude and uncertainty of dynamic topography change. We find coherent trends but also large variability among the different models, reflecting uncertainties in mantle density and viscosity structure, and in the appropriate coupling between mantle flow and surface plates. We make predictions for key sea level sites as well as discuss the effect of the dynamic topography correction on the observed elevation of a global database of 280 LIG sea level indicators. We find that (1) predicted deflections are significantly correlated (> 95% probability) with the elevation of sea level markers, (2) they are consistent with construction and preservation attributes across different sea level marker types, and (3) correcting for the effects of dynamic topography reduces the variability among marker elevations. We conclude that a dynamic topography signal is present in the elevation of LIG sea level records, and that the signal must be accounted for in any effort to determine peak global mean sea level during this time to within an accuracy of several meters.

  9. The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development.

    PubMed

    Martín-Bermudo, Maria-Dolores; Bardet, Pierre-Luc; Bellaïche, Yohanns; Malartre, Marianne

    2015-04-15

    Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types. We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development. Accordingly, decreasing EGFR signalling in vav mutant eyes restores retinal organisation and rescues most vav mutant phenotypes. Second, using live imaging in the pupal retina, we observe that vav mutant cells do not form stable adherens junctions, causing various defects, such as recruitment of extra primary pigment cells. In agreement with this role in junction dynamics, we observe that these phenotypes can be exacerbated by lowering DE-Cadherin or Cindr levels. Taken together, our findings establish that Vav acts at multiple times during eye development to prevent excessive cell recruitment by limiting EGFR signalling and by regulating junction dynamics to ensure the correct patterning and morphogenesis of the Drosophila eye. © 2015. Published by The Company of Biologists Ltd.

  10. Analog filtering of large solvent signals for improved dynamic range in high-resolution NMR.

    PubMed

    Redfield, A G; Kunz, S D

    1998-01-01

    The large solvent signal from samples in H2O solvent still challenges the dynamic range capability of any spectrometer. The solvent signal can be largely removed with a pair of simple resistor-capacitor (RC) high-pass filters when the solvent frequency is set at center band (zero frequency) using quadrature detection, with RC approximately 0.5 ms. However, an approximately 0.5-ms transient remains at initial time, which we reduce fourfold for a short time only, just before the A/D converter, by means of a variable-gain amplifier, and later restore with software. This modification can result in a nearly fourfold increase in dynamic range. When we converted to a frequency-shifted mode (A. G. Redfield and S. D. Kunz, 1994, J. Magn. Reson. A 108, 234-237) we replaced the RC high-pass filter with a quadrature feedback notch filter tuned to the solvent frequency (5.06 kHz). This filter is an example of a class of two-input/two-output filters which maintain the spectral integrity (image-free character) of quadrature signals. Digital filters of the same type are also considered briefly. We discuss the implications of these ideas for spectrometer input design, including schemes for elimination of radiation damping, and effects of probe bandwidth on extreme oversampling.

  11. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies

    PubMed Central

    Kolch, Walter; Kholodenko, Boris N.; Ambrosi, Cristina De; Barla, Annalisa; Biganzoli, Elia M.; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-01-01

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis. We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions. Starting from an initial “physiologic condition”, the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model. Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal. PMID:25671297

  12. High-throughput microfluidic single-cell analysis pipeline for studies of signaling dynamics.

    PubMed

    Kellogg, Ryan A; Gómez-Sjöberg, Rafael; Leyrat, Anne A; Tay, Savaş

    2014-07-01

    Time-dependent analysis of dynamic processes in single live cells is a revolutionary technique for the quantitative studies of signaling networks. Here we describe an experimental pipeline and associated protocol that incorporate microfluidic cell culture, precise stimulation of cells with signaling molecules or drugs, live-cell microscopy, computerized cell tracking, on-chip staining of key proteins and subsequent retrieval of cells for high-throughput gene expression analysis using microfluidic quantitative PCR (qPCR). Compared with traditional culture dish approaches, this pipeline enhances experimental precision and throughput by orders of magnitude and introduces much-desired new capabilities in cell and fluid handling, thus representing a major step forward in dynamic single-cell analysis. A combination of microfluidic membrane valves, automation and a streamlined protocol now enables a single researcher to generate 1 million data points on single-cell protein localization within 1 week, in various cell types and densities, under 48 predesigned experimental conditions selected from different signaling molecules or drugs, their doses, timings and combinations.

  13. Analog Filtering of Large Solvent Signals for Improved Dynamic Range in High-Resolution NMR

    NASA Astrophysics Data System (ADS)

    Redfield, A. G.; Kunz, S. D.

    1998-01-01

    The large solvent signal from samples in H2O solvent still challenges the dynamic range capability of any spectrometer. The solvent signal can be largely removed with a pair of simple resistor-capacitor (RC) high-pass filters when the solvent frequency is set at center band (zero frequency) using quadrature detection, withRC∼ 0.5 ms. However, an ∼0.5-ms transient remains at initial time, which we reduce fourfold for a short time only, just before the A/D converter, by means of a variable-gain amplifier, and later restore with software. This modification can result in a nearly fourfold increase in dynamic range. When we converted to a frequency-shifted mode (A. G. Redfield and S. D. Kunz, 1994,J. Magn. Reson. A108, 234-237) we replaced theRChigh-pass filter with a quadrature feedback notch filter tuned to the solvent frequency (5.06 kHz). This filter is an example of a class of two-input/two-output filters which maintain the spectral integrity (image-free character) of quadrature signals. Digital filters of the same type are also considered briefly. We discuss the implications of these ideas for spectrometer input design, including schemes for elimination of radiation damping, and effects of probe bandwidth on extreme oversampling.

  14. Signaling and Dynamic Actin Responses of B Cells on Topographical Substrates

    NASA Astrophysics Data System (ADS)

    Ketchum, Christina; Sun, Xiaoyu; Fourkas, John; Song, Wenxia; Upadhyaya, Arpita

    B cells become activated upon physical contact with antigen on the surface of antigen presenting cells, such as dendritic cells. Binding of the B cell receptor with antigen initiates actin-mediated spreading of B cells, signaling cascades and eventually infection fighting antibodies. Lymphocytes, including B cells and T cells, have been shown to be responsive to the physical parameters of the contact surface, such as antigen mobility and substrate stiffness. However the roll of surface topography on lymphocyte function is unknown. Here we investigate the degree to which substrate topography controls actin-mediated spreading and B cell activation using nano-fabricated surfaces and live cell imaging. The model topographical system consists of 600 nanometer tall ridges with spacing varying between 800 nanometers and 5 micrometers. Using TIRF imaging we observe actin dynamics, B cell receptor motion and calcium signaling of B cells as they spread on the ridged substrates. We show that the spacing between ridges had a strong effect on the dynamics of actin and calcium influx on B cells. Our results indicate that B cells are highly sensitive to surface topography during cell spreading and signaling activation.

  15. Measuring Dynamic Signals with Direct Sensor-to-Microcontroller Interfaces Applied to a Magnetoresistive Sensor

    PubMed Central

    Sifuentes, Ernesto; Gonzalez-Landaeta, Rafael; Cota-Ruiz, Juan; Reverter, Ferran

    2017-01-01

    This paper evaluates the performance of direct interface circuits (DIC), where the sensor is directly connected to a microcontroller, when a resistive sensor subjected to dynamic changes is measured. The theoretical analysis provides guidelines for the selection of the components taking into account both the desired resolution and the bandwidth of the input signal. Such an analysis reveals that there is a trade-off between the sampling frequency and the resolution of the measurement, and this depends on the selected value of the capacitor that forms the RC circuit together with the sensor resistance. This performance is then experimentally proved with a DIC measuring a magnetoresistive sensor exposed to a magnetic field of different frequencies, amplitudes, and waveforms. A sinusoidal magnetic field up to 1 kHz can be monitored with a resolution of eight bits and a sampling frequency of around 10 kSa/s. If a higher resolution is desired, the sampling frequency has to be lower, thus limiting the bandwidth of the dynamic signal under measurement. The DIC is also applied to measure an electrocardiogram-type signal and its QRS complex is well identified, which enables the estimation, for instance, of the heart rate. PMID:28524078

  16. Measuring Dynamic Signals with Direct Sensor-to-Microcontroller Interfaces Applied to a Magnetoresistive Sensor.

    PubMed

    Sifuentes, Ernesto; Gonzalez-Landaeta, Rafael; Cota-Ruiz, Juan; Reverter, Ferran

    2017-05-18

    This paper evaluates the performance of direct interface circuits (DIC), where the sensor is directly connected to a microcontroller, when a resistive sensor subjected to dynamic changes is measured. The theoretical analysis provides guidelines for the selection of the components taking into account both the desired resolution and the bandwidth of the input signal. Such an analysis reveals that there is a trade-off between the sampling frequency and the resolution of the measurement, and this depends on the selected value of the capacitor that forms the RC circuit together with the sensor resistance. This performance is then experimentally proved with a DIC measuring a magnetoresistive sensor exposed to a magnetic field of different frequencies, amplitudes, and waveforms. A sinusoidal magnetic field up to 1 kHz can be monitored with a resolution of eight bits and a sampling frequency of around 10 kSa/s. If a higher resolution is desired, the sampling frequency has to be lower, thus limiting the bandwidth of the dynamic signal under measurement. The DIC is also applied to measure an electrocardiogram-type signal and its QRS complex is well identified, which enables the estimation, for instance, of the heart rate.

  17. Super wavelet for sEMG signal extraction during dynamic fatiguing contractions.

    PubMed

    Al-Mulla, Mohamed R; Sepulveda, Francisco

    2015-01-01

    In this research an algorithm was developed to classify muscle fatigue content from dynamic contractions, by using a genetic algorithm (GA) and a pseudo-wavelet function. Fatiguing dynamic contractions of the biceps brachii were recorded using Surface Electromyography (sEMG) from thirteen subjects. Labelling the signal into two classes (Fatigue and Non-Fatigue) aided in the training and testing phase. The genetic algorithm was used to develop a pseudo-wavelet function that can optimally decompose the sEMG signal and classify the fatigue content of the signal. The evolved pseudo wavelet was tuned using the decomposition of 70% of the sEMG trials. 28 independent pseudo-wavelet evolution were run, after which the best run was selected and then tested on the remaining 30% of the trials to measure the classification performance. Results show that the evolved pseudo-wavelet improved the classification rate of muscle fatigue by 4.45 percentage points to 14.95 percentage points when compared to other standard wavelet functions (p<0.05), giving an average correct classification of 87.90%.

  18. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

    PubMed

    Tortolina, Lorenzo; Duffy, David J; Maffei, Massimo; Castagnino, Nicoletta; Carmody, Aimée M; Kolch, Walter; Kholodenko, Boris N; De Ambrosi, Cristina; Barla, Annalisa; Biganzoli, Elia M; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-03-10

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis.We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions.Starting from an initial "physiologic condition", the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model.Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal.

  19. Emergence of complex dynamics in a simple model of signaling networks

    PubMed Central

    Amaral, Luís A. N.; Díaz-Guilera, Albert; Moreira, Andre A.; Goldberger, Ary L.; Lipsitz, Lewis A.

    2004-01-01

    Various physical, social, and biological systems generate complex fluctuations with correlations across multiple time scales. In physiologic systems, these long-range correlations are altered with disease and aging. Such correlated fluctuations in living systems have been attributed to the interaction of multiple control systems; however, the mechanisms underlying this behavior remain unknown. Here, we show that a number of distinct classes of dynamical behaviors, including correlated fluctuations characterized by 1/f scaling of their power spectra, can emerge in networks of simple signaling units. We found that, under general conditions, complex dynamics can be generated by systems fulfilling the following two requirements, (i) a “small-world” topology and (ii) the presence of noise. Our findings support two notable conclusions. First, complex physiologic-like signals can be modeled with a minimal set of components; and second, systems fulfilling conditions i and ii are robust to some degree of degradation (i.e., they will still be able to generate 1/f dynamics). PMID:15505227

  20. Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states

    PubMed Central

    Adamson, Antony; Boddington, Christopher; Downton, Polly; Rowe, William; Bagnall, James; Lam, Connie; Maya-Mendoza, Apolinar; Schmidt, Lorraine; Harper, Claire V.; Spiller, David G.; Rand, David A.; Jackson, Dean A.; White, Michael R. H.; Paszek, Pawel

    2016-01-01

    Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation. PMID:27381163

  1. Static and dynamic analyses on the MFTF (Mirror Fusion Test Facility)-B Axicell Vacuum Vessel System: Final report

    SciTech Connect

    Ng, D.S.

    1986-09-01

    The Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) is a large-scale, tandem-mirror-fusion experiment. MFTF-B comprises many highly interconnected systems, including a magnet array and a vacuum vessel. The vessel, which houses the magnet array, is supported by reinforced concrete piers and steel frames resting on an array of foundations and surrounded by a 7-ft-thick concrete shielding vault. The Pittsburgh-Des Moines (PDM) Corporation, which was awarded the contract to design and construct the vessel, carried out fixed-base static and dynamic analyses of a finite-element model of the axicell vessel and magnet systems, including the simulation of various loading conditions and three postulated earthquake excitations. Meanwhile, LLNL monitored PDM's analyses with modeling studies of its own, and independently evaluated the structural responses of the vessel in order to define design criteria for the interface members and other project equipment. The assumptions underlying the finite-element model and the behavior of the axicell vessel are described in detail in this report, with particular emphasis placed on comparing the LLNL and PDM studies and on analyzing the fixed-base behavior with the soil-structure interaction, which occurs between the vessel and the massive concrete vault wall during a postulated seismic event. The structural members that proved sensitive to the soil effect are also reevaluated.

  2. Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

    PubMed

    Hall, Benjamin A; Armitage, Judith P; Sansom, Mark S P

    2011-10-01

    Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors.

  3. Beech Fructification and Bank Vole Population Dynamics - Combined Analyses of Promoters of Human Puumala Virus Infections in Germany

    PubMed Central

    Reil, Daniela; Imholt, Christian; Eccard, Jana Anja; Jacob, Jens

    2015-01-01

    The transmission of wildlife zoonoses to humans depends, amongst others, on complex interactions of host population ecology and pathogen dynamics within host populations. In Europe, the Puumala virus (PUUV) causes nephropathia epidemica in humans. In this study we investigated complex interrelations within the epidemic system of PUUV and its rodent host, the bank vole (Myodes glareolus). We suggest that beech fructification and bank vole abundance are both decisive factors affecting human PUUV infections. While rodent host dynamics are expected to be directly linked to human PUUV infections, beech fructification is a rather indirect predictor by serving as food source for PUUV rodent hosts. Furthermore, we examined the dependence of bank vole abundance on beech fructification. We analysed a 12-year (2001-2012) time series of the parameters: beech fructification (as food resource for the PUUV host), bank vole abundance and human incidences from 7 Federal States of Germany. For the first time, we could show the direct interrelation between these three parameters involved in human PUUV epidemics and we were able to demonstrate on a large scale that human PUUV infections are highly correlated with bank vole abundance in the present year, as well as beech fructification in the previous year. By using beech fructification and bank vole abundance as predictors in one model we significantly improved the degree of explanation of human PUUV incidence. Federal State was included as random factor because human PUUV incidence varies considerably among states. Surprisingly, the effect of rodent abundance on human PUUV infections is less strong compared to the indirect effect of beech fructification. Our findings are useful to facilitate the development of predictive models for host population dynamics and the related PUUV infection risk for humans and can be used for plant protection and human health protection purposes. PMID:26214509

  4. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    SciTech Connect

    Graber, Harry L. Xu, Yong; Barbour, Randall L.; Al abdi, Rabah; Asarian, Armand P.; Pappas, Peter J.; Dresner, Lisa; Patel, Naresh; Jagarlamundi, Kuppuswamy; Solomon, William B.

    2015-11-15

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  5. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    PubMed Central

    Graber, Harry L.; Al abdi, Rabah; Xu, Yong; Asarian, Armand P.; Pappas, Peter J.; Dresner, Lisa; Patel, Naresh; Jagarlamundi, Kuppuswamy; Solomon, William B.; Barbour, Randall L.

    2015-01-01

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  6. Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses

    PubMed Central

    Petrenko, Natalia; Chereji, Raˇzvan V.; McClean, Megan N.; Morozov, Alexandre V.; Broach, James R.

    2013-01-01

    All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to “hedge their bets” in responding to an uncertain future, and to balance growth and survival in an unpredictable environment. PMID:23615444

  7. Dynamic Faraday cup signal analysis and the measurement of energetic ions emitted by plasma focus

    NASA Astrophysics Data System (ADS)

    Pestehe, S. J.; Mohammadnejad, M.; Irani Mobaraki, S.

    2014-03-01

    A theoretical model is developed to study the signals from a typical dynamic Faraday cup, and using this model the output signals from this structure are obtained. A detailed discussion on the signal structure, using different experimental conditions, is also given. It is argued that there is a possibility of determining the total charge of the generated ion pulse, the maximum velocity of the ions, ion velocity distribution, and the number of ion species for mixed working gases, under certain conditions. In addition, the number of different ionization stages, the number of different pinches in one shot, and the number of different existing acceleration mechanisms can also be determined provided that the mentioned conditions being satisfied. An experiment is carried out on the Filippov type 90 kJ Sahand plasma focus using Ar as the working gas at the pressure of 0.25 Torr. The data from a typical shot are fitted to a signal from the model and the total charge of the related energetic ion pulse is deduced using the values of the obtained fit parameters. Good agreement between the obtained amount of the total charge and the values obtained during other experiments on the same plasma focus device is observed.

  8. Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses.

    PubMed

    Petrenko, Natalia; Chereji, Razvan V; McClean, Megan N; Morozov, Alexandre V; Broach, James R

    2013-06-01

    All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to "hedge their bets" in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.

  9. ACTIN DEPOLYMERIZING FACTOR4 regulates actin dynamics during innate immune signaling in Arabidopsis.

    PubMed

    Henty-Ridilla, Jessica L; Li, Jiejie; Day, Brad; Staiger, Christopher J

    2014-01-01

    Conserved microbe-associated molecular patterns (MAMPs) are sensed by pattern recognition receptors (PRRs) on cells of plants and animals. MAMP perception typically triggers rearrangements to actin cytoskeletal arrays during innate immune signaling. However, the signaling cascades linking PRR activation by MAMPs to cytoskeleton remodeling are not well characterized. Here, we developed a system to dissect, at high spatial and temporal resolution, the regulation of actin dynamics during innate immune signaling in plant cells. Within minutes of MAMP perception, we detected changes to single actin filament turnover in epidermal cells treated with bacterial and fungal MAMPs. These MAMP-induced alterations phenocopied an ACTIN DEPOLYMERIZING FACTOR4 (ADF4) knockout mutant. Moreover, actin arrays in the adf4 mutant were unresponsive to a bacterial MAMP, elf26, but responded normally to the fungal MAMP, chitin. Together, our data provide strong genetic and cytological evidence for the inhibition of ADF activity regulating actin remodeling during innate immune signaling. This work is the first to directly link an ADF/cofilin to the cytoskeletal rearrangements elicited directly after pathogen perception in plant or mammalian cells.

  10. Dynamic Faraday cup signal analysis and the measurement of energetic ions emitted by plasma focus

    SciTech Connect

    Pestehe, S. J. Mohammadnejad, M.; Irani Mobaraki, S.

    2014-03-15

    A theoretical model is developed to study the signals from a typical dynamic Faraday cup, and using this model the output signals from this structure are obtained. A detailed discussion on the signal structure, using different experimental conditions, is also given. It is argued that there is a possibility of determining the total charge of the generated ion pulse, the maximum velocity of the ions, ion velocity distribution, and the number of ion species for mixed working gases, under certain conditions. In addition, the number of different ionization stages, the number of different pinches in one shot, and the number of different existing acceleration mechanisms can also be determined provided that the mentioned conditions being satisfied. An experiment is carried out on the Filippov type 90 kJ Sahand plasma focus using Ar as the working gas at the pressure of 0.25 Torr. The data from a typical shot are fitted to a signal from the model and the total charge of the related energetic ion pulse is deduced using the values of the obtained fit parameters. Good agreement between the obtained amount of the total charge and the values obtained during other experiments on the same plasma focus device is observed.

  11. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    SciTech Connect

    Stevens, Mark A.; Pfeiffer, Janet R.; Wilson, Bridget S.; Timlin, Jerilyn Ann; Thomas, James L.; Lidke, Keith A.; Spendier, Kathrin; Oliver, Janet M.; Carroll-Portillo, Amanda; Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  12. Reporting from the Field: Genetically Encoded Fluorescent Reporters Uncover Signaling Dynamics in Living Biological Systems

    PubMed Central

    Mehta, Sohum; Zhang, Jin

    2015-01-01

    Real-time visualization of a wide range of biochemical processes in living systems is being made possible through the development and application of genetically encoded fluorescent reporters. These versatile biosensors have proven themselves tailor-made to the study of signal transduction, and in this review, we discuss some of the unique insights that they continue to provide regarding the spatial organization and dynamic regulation of intracellular signaling networks. In addition, we explore the more recent push to expand the scope of biological phenomena that can be monitored using these reporters, while also considering the potential to integrate this highly adaptable technology with a number of emerging techniques that may significantly broaden our view of how networks of biochemical processes shape larger biological phenomena. PMID:21495849

  13. Aurora A drives early signalling and vesicle dynamics during T-cell activation.

    PubMed

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B; Sánchez-Madrid, Francisco

    2016-04-19

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.

  14. The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation

    PubMed Central

    Lee, Semin; Bolanos-Garcia, Victor M.

    2014-01-01

    The control of chromosome segregation relies on the spindle assembly checkpoint (SAC), a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling. PMID:25324779

  15. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    PubMed Central

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  16. Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect

    PubMed Central

    Sachs, Lena; Chen, Yen-Ta; Drechsler, Axel; Lynch, Jeremy A; Panfilio, Kristen A; Lässig, Michael; Berg, Johannes; Roth, Siegfried

    2015-01-01

    Toll-dependent patterning of the dorsoventral axis in Drosophila represents one of the best understood gene regulatory networks. However, its evolutionary origin has remained elusive. Outside the insects Toll is not known for a patterning function, but rather for a role in pathogen defense. Here, we show that in the milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more than 350 million years ago, Toll is only required to polarize a dynamic BMP signaling network. A theoretical model reveals that this network has self-regulatory properties and that shallow Toll signaling gradients are sufficient to initiate axis formation. Such gradients can account for the experimentally observed twinning of insect embryos upon egg fragmentation and might have evolved from a state of uniform Toll activity associated with protecting insect eggs against pathogens. DOI: http://dx.doi.org/10.7554/eLife.05502.001 PMID:25962855

  17. Dynamics of the Bingham Canyon Mine landslides from seismic signal analysis

    NASA Astrophysics Data System (ADS)

    Hibert, Clément; Ekström, Göran; Stark, Colin P.

    2014-07-01

    Joint interpretation of long- and short-period seismic signals generated by landslides sheds light on the dynamics of slope failure, providing constraints on landslide initiation and termination and on the main phases of acceleration and deceleration. We carry out a combined analysis of the seismic signals generated by two massive landslides that struck the Bingham Canyon Mine pit on 10 April 2013. Inversion of the long-period waveforms yields time series for the bulk landslide forces and momenta, from which we deduce runout trajectories consistent with the deposit morphology. Comparing these time series with the short-period seismic data, we are able to infer when and where major changes take place in landslide momentum along the runout path. This combined analysis points to a progressive fracturing of the masses during acceleration indicates that deceleration starts the moment they reach the pit floor and suggests that the bulk movement is stopped by a topographic barrier.

  18. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes

    PubMed Central

    Curtis, Janelle M.R.

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  19. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes.

    PubMed

    Naujokaitis-Lewis, Ilona; Curtis, Janelle M R

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  20. Variability of a dynamic visual signal: the fiddler crab claw-waving display.

    PubMed

    How, Martin J; Zeil, Jochen; Hemmi, Jan M

    2009-01-01

    Fiddler crabs use elaborate, species-specific claw-waving displays to communicate with rivals and mates. However, detailed comparative studies of fiddler crab signal structure and structural variations are lacking. This paper provides an analysis of the claw-waving displays of seven Australian species of fiddler crab, Uca mjoebergi, U. perplexa, U. polita, U. seismella, U. signata, U. elegans and U. vomeris. We used digital video to record and analyse the fine-scale spatiotemporal properties of these movement-based visual signals. We found that the structure and timing of the displays is species-specific, exhibiting inter-specific differences that follow phylogenetic relationships. The displays showed intra-specific variation according to individual identity, geographic location and fine-scale behavioural context. The observed differences and variations are discussed in the light of the evolutionary forces that may shape their design.

  1. Edge-based sensitivity analysis of signaling networks by using Boolean dynamics.

    PubMed

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2016-09-01

    Biological networks are composed of molecular components and their interactions represented by nodes and edges, respectively, in a graph model. Based on this model, there were many studies with respect to effects of node-based mutations on the network dynamics, whereas little attention was paid to edgetic mutations so far. In this paper, we defined an edgetic sensitivity measure that quantifies how likely a converging attractor is changed by edge-removal mutations in a Boolean network model. Through extensive simulations based on that measure, we found interesting properties of highly sensitive edges in both random and real signaling networks. First, the sensitive edges in random networks tend to link two end nodes both of which are susceptible to node-knockout mutations. Interestingly, it was analogous to an observation that the sensitive edges in human signaling networks are likely to connect drug-target genes. We further observed that the edgetic sensitivity predicted drug-targets better than the node-based sensitivity. In addition, the sensitive edges showed distinguished structural characteristics such as a lower connectivity, more involving feedback loops and a higher betweenness. Moreover, their gene-ontology enrichments were clearly different from the other edges. We also observed that genes incident to the highly sensitive interactions are more central by forming a considerably large connected component in human signaling networks. Finally, we validated our approach by showing that most sensitive interactions are promising edgetic drug-targets in p53 cancer and T-cell apoptosis networks. Taken together, the edgetic sensitivity is valuable to understand the complex dynamics of signaling networks. kwonyk@ulsan.ac.kr Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Signalling crosstalk at the leading edge controls tissue closure dynamics in the Drosophila embryo.

    PubMed

    Rousset, Raphaël; Carballès, Fabrice; Parassol, Nadège; Schaub, Sébastien; Cérézo, Delphine; Noselli, Stéphane

    2017-02-01

    Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGFβ/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we sought out new JNK target genes through a genomic approach: 25 were identified of which 8 are specifically expressed in the LE, similarly to decapentaplegic or puckered. Quantitative in situ gene profiling of this new set of LE genes reveals complex patterning of the LE along the AP axis, involving a three-way interplay between the JNK pathway, segmentation and HOX genes. Patterning of the LE into discrete domains appears essential for coordination of tissue sealing dynamics. Loss of anterior or posterior HOX gene function leads to strongly delayed and asymmetric DC, due to incorrect zipping in their respective functional domain. Therefore, in addition to significantly increasing the number of JNK target genes identified so far, our results reveal that the LE is a highly heterogeneous morphogenetic organizer, sculpted through crosstalk between JNK, segmental and AP signalling. This fine-tuning regulatory mechanism is essential to coordinate morphogenesis and dynamics of tissue sealing.

  3. Multiple Model-Informed Open-Loop Control of Uncertain Intracellular Signaling Dynamics

    PubMed Central

    Perley, Jeffrey P.; Mikolajczak, Judith; Harrison, Marietta L.; Buzzard, Gregery T.; Rundell, Ann E.

    2014-01-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  4. Signalling crosstalk at the leading edge controls tissue closure dynamics in the Drosophila embryo

    PubMed Central

    Carballès, Fabrice; Parassol, Nadège; Schaub, Sébastien; Cérézo, Delphine; Noselli, Stéphane

    2017-01-01

    Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGFβ/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we sought out new JNK target genes through a genomic approach: 25 were identified of which 8 are specifically expressed in the LE, similarly to decapentaplegic or puckered. Quantitative in situ gene profiling of this new set of LE genes reveals complex patterning of the LE along the AP axis, involving a three-way interplay between the JNK pathway, segmentation and HOX genes. Patterning of the LE into discrete domains appears essential for coordination of tissue sealing dynamics. Loss of anterior or posterior HOX gene function leads to strongly delayed and asymmetric DC, due to incorrect zipping in their respective functional domain. Therefore, in addition to significantly increasing the number of JNK target genes identified so far, our results reveal that the LE is a highly heterogeneous morphogenetic organizer, sculpted through crosstalk between JNK, segmental and AP signalling. This fine-tuning regulatory mechanism is essential to coordinate morphogenesis and dynamics of tissue sealing. PMID:28231245

  5. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    PubMed

    Perley, Jeffrey P; Mikolajczak, Judith; Harrison, Marietta L; Buzzard, Gregery T; Rundell, Ann E

    2014-04-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  6. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling

    PubMed Central

    Bao, Li; Avshalumov, Marat V.; Patel, Jyoti C.; Lee, Christian R.; Miller, Evan W.; Chang, Christopher J.; Rice, Margaret E.

    2010-01-01

    Hydrogen peroxide (H2O2) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H2O2 signaling, which activates ATP-sensitive potassium (KATP) channels to inhibit dopamine release. However, the origin of this modulatory H2O2 has been elusive. Here we addressed three possible sources of H2O2 produced for rapid neuronal signaling in striatum: mitochondrial respiration; monoamine oxidase (MAO); and NADPH oxidase (Nox). Evoked dopamine release in guinea-pig striatal slices was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence imaging of H2O2 and tissue analysis of ATP, we found that co-application of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H2O2 production, but maintained tissue ATP content. Strikingly, co-application of rotenone and succinate also prevented glutamate-dependent regulation of dopamine release, implicating mitochondrial H2O2 in release modulation. By contrast, inhibitors of MAO or Nox had no effect on dopamine release, suggesting a limited role for these metabolic enzymes in rapid H2O2 production in the striatum. These data provide the first demonstration that respiring mitochondria are the primary source of H2O2 generation for dynamic neuronal signaling. PMID:19605638

  7. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling.

    PubMed

    Bao, Li; Avshalumov, Marat V; Patel, Jyoti C; Lee, Christian R; Miller, Evan W; Chang, Christopher J; Rice, Margaret E

    2009-07-15

    Hydrogen peroxide (H(2)O(2)) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H(2)O(2) signaling, which activates ATP-sensitive potassium (K(ATP)) channels to inhibit dopamine release. However, the origin of this modulatory H(2)O(2) has been elusive. Here we addressed three possible sources of H(2)O(2) produced for rapid neuronal signaling in striatum: mitochondrial respiration, monoamine oxidase (MAO), and NADPH oxidase (Nox). Evoked dopamine release in guinea-pig striatal slices was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence imaging of H(2)O(2) and tissue analysis of ATP, we found that coapplication of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H(2)O(2) production, but maintained tissue ATP content. Strikingly, coapplication of rotenone and succinate also prevented glutamate-dependent regulation of dopamine release, implicating mitochondrial H(2)O(2) in release modulation. In contrast, inhibitors of MAO or Nox had no effect on dopamine release, suggesting a limited role for these metabolic enzymes in rapid H(2)O(2) production in the striatum. These data provide the first demonstration that respiring mitochondria are the primary source of H(2)O(2) generation for dynamic neuronal signaling.

  8. Molecular Dynamics Investigation of a Mechanism of Allosteric Signal Transmission in Ribosomes.

    PubMed

    Makarov, G I; Golovin, A V; Sumbatyan, N V; Bogdanov, A A

    2015-08-01

    The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed.

  9. Signal analysis applications of nonlinear dynamics and higher-order statistics

    NASA Astrophysics Data System (ADS)

    Solinsky, James C.; Feeney, John J.

    1994-03-01

    The use of higher-order statistics (HOS) in acoustic, and financial signal analysis applications is outlined in theory and followed with specific data examples. HOS analysis is used to identify data regions of interest, and nonlinear dynamics (ND) analysis is used in a 4D embedded space to show structural density changes resulting from the HOS regions. A second-order statistical comparison is made with the same data processed to have random Fourier phase, since the HOS information is contained in this nonrandom phase. These empirical results indicate that HOS data regions are structural distortions to a second-order planar disk in the 4D ND analysis space.

  10. Research of time discrimination circuits for PMT signal readout over large dynamic range in LHAASO WCDA

    NASA Astrophysics Data System (ADS)

    Ma, C.; Zhao, L.; Dong, R.; Jiang, Z.; Chu, S.; Gao, X.; Liu, S.; An, Q.

    2016-11-01

    In the readout electronics of the Water Cerenkov Detector Array (WCDA) in the Large High Altitude Air Shower Observatory (LHAASO), both high-resolution charge and time measurement are required over a dynamic range from 1 photoelectron (P.E.) to 4000 P.E. for the PMT signal readout. In this paper, we present our work on the design of time discrimination circuits in LHAASO WCDA, especially on improvement to reduce the circuit dead time. Several approaches were studied through analysis and simulations, and actual circuits were designed and tested in the laboratory to evaluate the performance. Test results indicate that a time resolution better than 500 ps RMS is achieved in the whole large dynamic range, and the circuit dead time is successfully reduced to less than 200 ns.

  11. Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

    NASA Astrophysics Data System (ADS)

    Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

    2017-04-01

    Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

  12. Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function.

    PubMed

    Kembro, Jackelyn M; Cortassa, Sonia; Aon, Miguel A

    2014-01-01

    The time-keeping properties bestowed by oscillatory behavior on functional rhythms represent an evolutionarily conserved trait in living systems. Mitochondrial networks function as timekeepers maximizing energetic output while tuning reactive oxygen species (ROS) within physiological levels compatible with signaling. In this work, we explore the potential for timekeeping functions dependent on mitochondrial dynamics with the validated two-compartment mitochondrial energetic-redox (ME-R) computational model, that takes into account (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix compartments, and (c) transport of ROS species between them. Herein, we describe that the ME-R model can exhibit highly complex oscillatory dynamics in energetic/redox variables and ROS species, consisting of at least five frequencies with modulated amplitudes and period according to power spectral analysis. By stability analysis we describe that the extent of steady state-as against complex oscillatory behavior-was dependent upon the abundance of Mn and Cu, Zn SODs, and their interplay with ROS production in the respiratory chain. Large parametric regions corresponding to oscillatory dynamics of increasingly complex waveforms were obtained at low Cu, Zn SOD concentration as a function of Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn SOD. Interestingly, the realm of complex oscillations was located at the edge between normal and pathological mitochondrial energetic behavior, and was characterized by oxidative stress. We conclude that complex oscillatory dynamics could represent a frequency- and amplitude-modulated H2O2 signaling mechanism that arises under intense oxidative stress. By modulating SOD, cells could have evolved an adaptive compromise between relative constancy and the flexibility required under stressful redox/energetic conditions.

  13. Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function

    PubMed Central

    Kembro, Jackelyn M.; Cortassa, Sonia; Aon, Miguel A.

    2014-01-01

    The time-keeping properties bestowed by oscillatory behavior on functional rhythms represent an evolutionarily conserved trait in living systems. Mitochondrial networks function as timekeepers maximizing energetic output while tuning reactive oxygen species (ROS) within physiological levels compatible with signaling. In this work, we explore the potential for timekeeping functions dependent on mitochondrial dynamics with the validated two-compartment mitochondrial energetic-redox (ME-R) computational model, that takes into account (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix compartments, and (c) transport of ROS species between them. Herein, we describe that the ME-R model can exhibit highly complex oscillatory dynamics in energetic/redox variables and ROS species, consisting of at least five frequencies with modulated amplitudes and period according to power spectral analysis. By stability analysis we describe that the extent of steady state—as against complex oscillatory behavior—was dependent upon the abundance of Mn and Cu, Zn SODs, and their interplay with ROS production in the respiratory chain. Large parametric regions corresponding to oscillatory dynamics of increasingly complex waveforms were obtained at low Cu, Zn SOD concentration as a function of Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn SOD. Interestingly, the realm of complex oscillations was located at the edge between normal and pathological mitochondrial energetic behavior, and was characterized by oxidative stress. We conclude that complex oscillatory dynamics could represent a frequency- and amplitude-modulated H2O2 signaling mechanism that arises under intense oxidative stress. By modulating SOD, cells could have evolved an adaptive compromise between relative constancy and the flexibility required under stressful redox

  14. Perturbation and nonlinear dynamic analysis of acoustic phonatory signal in Parkinsonian patients receiving deep brain stimulation

    PubMed Central

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A.; Wang, Emily Q.; Jiang, Jack J.

    2012-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D2), percent jitter, percent shimmer, SNR, F0, vF0, and vAm. The results indicated the following: The mean D2 of control PD patients was significantly higher than the mean D2 of non-pathologic subjects and patients who received deep brain stimulation. These results suggest an improvement in PD voice in treated patients. Many PD vocal samples in this study have type 2 signals containing subharmonics that may not be suitable for perturbation analysis but are suitable for nonlinear dynamic analysis, making the D2 results more reliable. These findings show that DBS may provide measurable improvement in patients with severe vocal impairment. Learning outcomes Readers will be able to: (1) identify the advantages of nonlinear dynamic analysis as a clinical tool to evaluate the aperiodic voice commonly found in patients with Parkinson’s disease, (2) describe in general the method of obtaining a correlation dimension measure from a voice sample and the significance of this measure in terms of specific voice signal properties, (3) consider the preliminary implications from nonlinear dynamic analysis of a positive DBS effect on Parkinsonian voice and the potential for further investigations using nonlinear dynamic analysis on the influence of gender, severity of disease, and combined treatments on Parkinsonian voice improvement. PMID:18433765

  15. Profiling the Dynamics of a Human Phosphorylome Reveals New Components in HGF/c-Met Signaling

    PubMed Central

    Wan, Jun; Xia, Shuli; Newman, Robert; Hu, Jianfei; Zhang, Jin; Hayward, S. Diane; Qian, Jiang; Laterra, John; Zhu, Heng

    2013-01-01

    Protein phosphorylation is a dynamic and reversible event that greatly influences cellular function. Identifying the key regulatory elements that determine cellular phenotypes during development and oncogenesis requires the ability to dynamically monitor proteome-wide events. Here, we report the development of a new strategy to monitor dynamic changes of protein phosphorylation in cells and tissues using functional protein microarrays as the readout. To demonstrate this technology's ability to identify condition-dependent phosphorylation events, human protein microarrays were incubated with lysates from cells or tissues under activation or inhibition of c-Met, a receptor tyrosine kinase involved in tissue morphogenesis and malignancy. By comparing the differences between the protein phosphorylation profiles obtained using the protein microarrays, we were able to recover many of the proteins that are known to be specifically activated (i.e., phosphorylated) upon c-Met activation by the hepatocyte growth factor (HGF). Most importantly, we discovered many proteins that were differentially phosphorylated by lysates from cells or tissues when the c-Met pathway was active. Using phosphorylation-specific antibodies, we were able to validate several candidate proteins as new downstream components of the c-Met signaling pathway in cells. We envision that this new approach, like its DNA microarray counterpart, can be further extended toward profiling dynamics of global protein phosphorylation under many different physiological conditions both in cellulo and in vivo in a high-throughput and cost-effective fashion. PMID:24023761

  16. Noise-driven signal transmission device using molecular dynamics of organic polymers

    NASA Astrophysics Data System (ADS)

    Asakawa, Naoki; Umemura, Koichiro; Fujise, Shinya; Yazawa, Koji; Shimizu, Tadashi; Tansho, Masataka; Kanki, Teruo; Tanaka, Hidekazu

    2014-01-01

    Stochastic threshold devices using a trap-filling transition (TFT) coupled with molecular dynamics in poly(3-alkylthiophene)s were fabricated as potential key devices for noise-driven bioinspired sensors and information processors. This article deals with variable-temperature direct current conductivity and alternating current impedance measurements for vertical-type device elements of Au/regioregular poly(3-decylthiophene) ((RR-P3DT) (thickness: 100 nm)/Au, which show multiple conducting states and quasi-stochastic transitions between these states. Noise measurements indicate the ω-2-type (if VVTFT) power spectral densities, where V and VTFT are an applied voltage and the voltage for TFT, respectively. The noise generation is due to the TFT associated with twist dynamics of π-conjugated polymers near the order-disorder phase transition (ODT). At 298 K, the quasi-stochastic behavior is more noticeable for RR-P3DT than poly(3-hexylthiophene). The quasi-stochastic property is employed to a stochastic one-directional signal transmitting device using optical-electric conversion. The dynamics of ODT for powder samples were also investigated by differential scanning calorimetry measurements and high-resolution solid-state C13 nuclear magnetic resonance spectroscopy, and the correlation of the molecular structure and dynamics with electric properties was discussed.

  17. A new measurement method for the dynamic resistance signal during the resistance spot welding process

    NASA Astrophysics Data System (ADS)

    Wang, Lijing; Hou, Yanyan; Zhang, Hongjie; Zhao, Jian; Xi, Tao; Qi, Xiangyang; Li, Yafeng

    2016-09-01

    To measure the dynamic resistance signal during the resistance spot welding process, some original work was carried out and a new measurement method was developed. Compared with the traditional method, using the instantaneous electrode voltage and welding current at peak current point in each half cycle, the resistance curve from the newly proposed method can provide more details of the dynamic resistance changes over time. To test the specific performance of the proposed method, a series of welding experiments were carried out and the tensile shear strengths of the weld samples were measured. Then, the measurement error of the proposed method was evaluated. Several features were extracted from the dynamic resistance curves. The correlations between the extracted features and weld strength were analyzed and the results show that these features are closely related to the weld strength and they can be used for welding quality monitoring. Moreover, the dynamic resistance curve from the newly proposed method can also be used to monitor some abnormal welding conditions.

  18. Comparative genomic and phylogenetic analyses reveal the evolution of the core two-component signal transduction systems in enterobacteria.

    PubMed

    Qi, Mingsheng; Sun, Feng-Jie; Caetano-Anollés, Gustavo; Zhao, Youfu

    2010-02-01

    The two-component signal transduction system (TCST) consists of a histidine kinase (HK) and a response regulator (RR). TCSTs play important roles in sensing and reacting to environmental changes, and in bacterial pathogenesis. Previously, we have identified and characterized TCSTs in Erwinia amylovora, a severe plant enterobacterial pathogen, at genome-wide level. Here we conducted a comparative genomic analysis of TCSTs in 53 genomes of 16 enterobacterial species. These species include important plant, animal, human, and insect pathogenic, saprophytic or symbiotic microorganisms. Comparative genomic analysis revealed that enterobacteria contain eight pairs of core TCSTs. Phylogenetic trees reconstructed from a concatenation of the core set of TCSTs from enterobacteria and for individual TCST proteins from species in Proteobacteria showed that most TCST protein trees in the Enterobacteriaceae or in species of the γ-Proteobacteria agreed well with that of the corresponding 16S rRNA gene. It also showed that co-evolutionary relationships existed between cognate partners of the HKs and RRs. Several core TCSTs were quite ancient and universal based on phylogenomic analysis of protein structures. These results indicate that the core TCSTs are relatively conserved, and suggest that these enterobacteria may have maintained their ancient core TCSTs and might acquire specific new TCSTs for their survival in different environments or hosts, or may have evolved new functionalities of the core TCSTs for adaptation to different ecological niches.

  19. Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells.

    PubMed

    Malec, Viktor; Coulson, Judy M; Urbé, Sylvie; Clague, Michael J

    2015-12-04

    The loss of function of the Von Hippel-Lindau (VHL) tumor suppressor leads to the development of hypervascular tumors, exemplified by clear-cell-type renal cell carcinoma (RCC). VHL governs the adaptive responses to fluctuation of oxygen levels largely through the regulated suppression of hypoxia inducible factors (HIFs). Here, we combine proteome and phospho-proteomic analysis of isogenic 786-O RCC (±VHL) cells to compare signatures that reflect hypoxia and/or loss of VHL. VHL-independent hypoxic responses, notably include up-regulation of phosphorylation at Ser232 on the pyruvate dehydrogenase α subunit that is known to promote glycolysis. Hypoxic responses governed by VHL include up-regulation of known biomarkers of RCC (e.g., GLUT1, NDRG1) and the signaling adaptor molecule IRS-2. Notably, we also observe down-regulation of linked-components associated with the Jacobs-Stewart cycle, including the intracellular carbonic anhydrase II (CA2), which governs cellular response to CO2 fluctuations that often accompany hypoxia in tumors. Further studies indicate an unusual mechanism of control for CA2 expression that, at least in part, reflects enhanced activity of the NFκB pathway, which is associated with loss of VHL.

  20. Identification of novel plant peroxisomal targeting signals by a combination of machine learning methods and in vivo subcellular targeting analyses.

    PubMed

    Lingner, Thomas; Kataya, Amr R; Antonicelli, Gerardo E; Benichou, Aline; Nilssen, Kjersti; Chen, Xiong-Yan; Siemsen, Tanja; Morgenstern, Burkhard; Meinicke, Peter; Reumann, Sigrun

    2011-04-01

    In the postgenomic era, accurate prediction tools are essential for identification of the proteomes of cell organelles. Prediction methods have been developed for peroxisome-targeted proteins in animals and fungi but are missing specifically for plants. For development of a predictor for plant proteins carrying peroxisome targeting signals type 1 (PTS1), we assembled more than 2500 homologous plant sequences, mainly from EST databases. We applied a discriminative machine learning approach to derive two different prediction methods, both of which showed high prediction accuracy and recognized specific targeting-enhancing patterns in the regions upstream of the PTS1 tripeptides. Upon application of these methods to the Arabidopsis thaliana genome, 392 gene models were predicted to be peroxisome targeted. These predictions were extensively tested in vivo, resulting in a high experimental verification rate of Arabidopsis proteins previously not known to be peroxisomal. The prediction methods were able to correctly infer novel PTS1 tripeptides, which even included novel residues. Twenty-three newly predicted PTS1 tripeptides were experimentally confirmed, and a high variability of the plant PTS1 motif was discovered. These prediction methods will be instrumental in identifying low-abundance and stress-inducible peroxisomal proteins and defining the entire peroxisomal proteome of Arabidopsis and agronomically important crop plants.

  1. I. Advances in NMR Signal Processing. II. Spin Dynamics in Quantum Dissipative Systems

    SciTech Connect

    Lin, Yung-Ya

    1998-11-01

    Part I. Advances in IVMR Signal Processing. Improvements of sensitivity and resolution are two major objects in the development of NMR/MRI. A signal enhancement method is first presented which recovers signal from noise by a judicious combination of a priordmowledge to define the desired feasible solutions and a set theoretic estimation for restoring signal properties that have been lost due to noise contamination. The effect of noise can be significantly mitigated through the process of iteratively modifying the noisy data set to the smallest degree necessary so that it possesses a collection of prescribed properties and also lies closest to the original data set. A novel detection-estimation scheme is then introduced to analyze noisy and/or strongly damped or truncated FIDs. Based on exponential modeling, the number of signals is detected based on information estimated using the matrix pencil method. theory and the spectral parameters are Part II. Spin Dynamics in body dipole-coupled systems Quantum Dissipative Systems. Spin dynamics in manyconstitutes one of the most fundamental problems in magnetic resonance and condensed-matter physics. Its many-spin nature precludes any rigorous treatment. ‘Therefore, the spin-boson model is adopted to describe in the rotating frame the influence of the dipolar local fields on a tagged spin. Based on the polaronic transform and a perturbation treatment, an analytical solution is derived, suggesting the existence of self-trapped states in the. strong coupling limit, i.e., when transverse local field >> longitudinal local field. Such nonlinear phenomena originate from the joint action of the lattice fluctuations and the reaction field. Under semiclassical approximation, it is found that the main effect of the reaction field is the renormalization of the Hamiltonian of interest. Its direct consequence is the two-step relaxation process: the spin is initially localized in a quasiequilibrium state, which is later detrapped by

  2. Quantitative Proteomic Analyses Identify ABA-Related Proteins and Signal Pathways in Maize Leaves under Drought Conditions.

    PubMed

    Zhao, Yulong; Wang, Yankai; Yang, Hao; Wang, Wei; Wu, Jianyu; Hu, Xiuli

    2016-01-01

    Drought stress is one of major factors resulting in maize yield loss. The roles of abscisic acid (ABA) have been widely studied in crops in response to drought stress. However, more attention is needed to identify key ABA-related proteins and also gain deeper molecular insights about drought stress in maize. Based on this need, the physiology and proteomics of the ABA-deficient maize mutant vp5 and its wild-type Vp5 under drought stress were examined and analyzed. Malondialdehyde content increased and quantum efficiency of photosystem II decreased under drought stress in both genotypes. However, the magnitude of the increase or decrease was significantly higher